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Sample records for fetal lung development

  1. MRI of normal and pathological fetal lung development.

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    Kasprian, Gregor; Balassy, Csilla; Brugger, Peter C; Prayer, Daniela

    2006-02-01

    Normal fetal lung development is a complex process influenced by mechanical and many biochemical factors. In addition to ultrasound, fetal magnetic resonance imaging (MRI) constitutes a new method to investigate this process in vivo during the second and third trimester. The techniques of MRI volumetry, assessment of signal intensities, and MRI spectroscopy of the fetal lung have been used to analyze this process and have already been applied clinically to identify abnormal fetal lung growth. Particularly in conditions such as oligohydramnios and congenital diaphragmatic hernia (CDH), pulmonary hypoplasia may be the cause of neonatal death. A precise diagnosis and quantification of compromised fetal lung development may improve post- and perinatal management. The main events in fetal lung development are reviewed and MR volumetric data from 106 normal fetuses, as well as different examples of pathological lung growth, are provided.

  2. MRI of normal and pathological fetal lung development

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    Kasprian, Gregor [University Clinic of Radiodiagnostics, Medical University of Vienna (Austria)]. E-mail: gregor.kasprian@meduniwien.ac.at; Balassy, Csilla [University Clinic of Radiodiagnostics, Medical University of Vienna (Austria); Brugger, Peter C. [Center of Anatomy and Cell Biology, Medical University of Vienna (Austria); Prayer, Daniela [University Clinic of Radiodiagnostics, Medical University of Vienna (Austria)

    2006-02-15

    Normal fetal lung development is a complex process influenced by mechanical and many biochemical factors. In addition to ultrasound, fetal magnetic resonance imaging (MRI) constitutes a new method to investigate this process in vivo during the second and third trimester. The techniques of MRI volumetry, assessment of signal intensities, and MRI spectroscopy of the fetal lung have been used to analyze this process and have already been applied clinically to identify abnormal fetal lung growth. Particularly in conditions such as oligohydramnios and congenital diaphragmatic hernia (CDH), pulmonary hypoplasia may be the cause of neonatal death. A precise diagnosis and quantification of compromised fetal lung development may improve post- and perinatal management. The main events in fetal lung development are reviewed and MR volumetric data from 106 normal fetuses, as well as different examples of pathological lung growth, are provided.

  3. MR assessment of fetal lung development using lung volumes and signal intensities

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    Keller, Thomas M.; Michel, Sven C.A.; Marincek, Borut [Institute of Diagnostic Radiology, University Hospital Zurich, Raemistrasse 100, 8091, Zurich (Switzerland); Rake, Annett; Wisser, Josef [Department of Obstetrics, University Hospital Zurich, Raemistrasse 100, 8091, Zurich (Switzerland); Seifert, Burkhardt [Department of Biostatistics, University of Zurich, Sumatrastrasse 30, 8006, Zurich (Switzerland); Kubik-Huch, Rahel A. [Institute of Diagnostic Radiology, University Hospital Zurich, Raemistrasse 100, 8091, Zurich (Switzerland); Institute of Radiology, Kantonsspital Baden, 5404, Baden (Switzerland)

    2004-06-01

    The purpose of this study was to evaluate the monitoring and diagnostic potential of MRI in fetal lung development and disease using lung volume and signal intensity changes through gestation. Thirty-five healthy fetuses (22-42 weeks) were examined on a 1.5- T MR system using sagittal T2w single-shot fast spin-echo imaging (TR indefinite, TE 90 ms, slice thickness/gap 3-5/0 mm, FOV 26-40 cm, NEX 0.5). Fetal body and lung were segmented manually and volumes calculated. Signal intensities (SI) of fetal lung and three reference values were measured on the section best displaying the lung. Regions of interests were defined by including the maximal organ area possible. The following SI ratios were generated: lung/liver, lung/amniotic fluid, lung/muscle, liver/fluid and liver/muscle. Volumes and ratios were correlated with gestational age. Data from seven fetuses with pulmonary pathology were compared with these normative values. Absolute lung volume varied from 12.3 to 143.5 cm{sup 3} in correlation with gestational age (P<0.001); lung volume relative to total body volume ranged from 1.6 to 5.0%, decreasing with gestational age (P=0.001). (orig.)

  4. MR ASSESSMENT OF LUNG DEVELOPMENT IN FETAL ANOMALIES USING RATIO OF LUNG TO LIVER SIGNAL INTENSITIES

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To evaluate the monitoring and diagnostic potential of MR in fetal lung development using lung signal intensity changes in the fetus. Methods The lung-to-liver intensity ratio was calculated by means of region-of-interest analysis in all 35 fetuses including 7 bilateral urinary anomalies, 9 unilateral urinary anomalies, 5 pulmonary anomalies, and 14 others. Results All fetuses with urinary anomalies and pulmonary anomalies showed low ratio of lung-to-liver signal intensity. Conclusion Low ratio of lung-to-liver signal intensity on MR imaging indicates pulmonary hypoplasia after 22 weeks' gestation.

  5. ROCK2 is involved in accelerated fetal lung development induced by in vivo lung distension.

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    Cloutier, Marc; Tremblay, Monique; Piedboeuf, Bruno

    2010-10-01

    Lung development is strongly influenced by its state of distension. For instance, increasing distension induced by fetal tracheal occlusion (TO) stimulates lung development. In contrast, oligohydramnios (OH) reduces lung distending forces and results in lung hypoplasia. We hypothesize that Rho/Rho-associated kinase (ROCK) pathway plays an important role as mechanosensor in vivo acting either directly or indirectly in the translation of increased distension into acceleration of lung growth. TO was done in fetal mice sacrificed either 3 or 24 hr later; in a subset of dam, fasudil, a specific ROCK inhibitor, or vehicle was injected intra-peritoneally. OH was done by puncture of the amniotic sac. ROCK2 protein levels were assessed by Western blot and immunohistochemistry (IHC); lung development was assessed by measuring the generation of distal respiratory airway. Significant differences were found in ROCK2 protein levels between TO and Sham-TO at 3 and 24 hr, but not for ROCK1. Indeed, IHC revealed that ROCK2 staining was sparse and restricted to a few mesenchymal cells in Sham-TO, whereas it was strong in acini of TO lungs. OH lungs expressed lower levels of ROCK2 in the acini when compared to untouched controls. In fasudil-treated animals, the degree of lung development following TO was significantly lower than in the group injected with vehicle. At the dose regimen used, fasudil did not affect normal lung development, as observed in the untouched animals. In summary, ROCK2 protein levels was affected by the degree of lung expansion and blunting ROCK activity abolished the response to increased lung distension, suggesting that ROCK is a key regulator in TO-induced accelerated lung development.

  6. N-Methyl-D-aspartate Receptor Excessive Activation Inhibited Fetal Rat Lung Development In Vivo and In Vitro

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    Zhengchang Liao

    2016-01-01

    Full Text Available Background. Intrauterine hypoxia is a common cause of fetal growth and lung development restriction. Although N-methyl-D-aspartate receptors (NMDARs are distributed in the postnatal lung and play a role in lung injury, little is known about NMDAR’s expression and role in fetal lung development. Methods. Real-time PCR and western blotting analysis were performed to detect NMDARs between embryonic days (E 15.5 and E21.5 in fetal rat lungs. NMDAR antagonist MK-801’s influence on intrauterine hypoxia-induced retardation of fetal lung development was tested in vivo, and NMDA’s direct effect on fetal lung development was observed using fetal lung organ culture in vitro. Results. All seven NMDARs are expressed in fetal rat lungs. Intrauterine hypoxia upregulated NMDARs expression in fetal lungs and decreased fetal body weight, lung weight, lung-weight-to-body-weight ratio, and radial alveolar count, whereas MK-801 alleviated this damage in vivo. In vitro experiments showed that NMDA decreased saccular circumference and area per unit and downregulated thyroid transcription factor-1 and surfactant protein-C mRNA expression. Conclusions. The excessive activation of NMDARs contributed to hypoxia-induced fetal lung development retardation and appropriate blockade of NMDAR might be a novel therapeutic strategy for minimizing the negative outcomes of prenatal hypoxia on lung development.

  7. [Fetal lung development on MRT. Normal course and impairment due to premature rupture of membranes].

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    Kasprian, G; Brugger, P C; Helmer, H; Langer, M; Balassy, C; Prayer, D

    2006-02-01

    A well-organized interplay between many molecular factors as well as mechanical forces influence fetal lung development. At the end of this complex process a sufficiently sized and structurally mature organ should ensure the postnatal survival of the newborn. Besides prenatal ultrasonography, magnetic resonance imaging (MRI) can now be used to investigate normal and pathological human lung growth in utero. Oligohydramnios, due to premature rupture of membranes (PROM), is an important risk factor for compromised fetal lung growth. In these situations MR volumetry can be used to measure the size of the fetal lung quite accurately. Together with the evaluation of lung signal intensities on T2-weighted sequences, fetuses with pulmonary hypoplasia can be readily detected.

  8. Differential response of the epithelium and interstitium in developing human fetal lung explants to hyperoxia.

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    Bustani, Porus; Hodge, Rachel; Tellabati, Ananth; Li, Juan; Pandya, Hitesh; Kotecha, Sailesh

    2006-03-01

    Hyperoxia is closely linked with the development of chronic lung disease of prematurity (CLD), but the exact mechanisms whereby hyperoxia alters the lung architecture in the developing lung remain largely unknown. We developed a fetal human lung organ culture model to investigate (a) the morphologic changes induced by hyperoxia and (b) whether hyperoxia resulted in differential cellular responses in the epithelium and interstitium. The effects of hyperoxia on lung morphometry were analyzed using computer-assisted image analysis. The lung architecture remained largely unchanged in normoxia lasting as long as 4 d. In contrast, hyperoxic culture of pseudoglandular fetal lungs resulted in significant dilatation of airways, thinning of the epithelium, and regression of the interstitium including the pulmonary vasculature. Although there were no significant differences in Ki67 between normoxic and hyperoxic lungs, activated caspase-3 was significantly increased in interstitial cells, but not epithelial cells, under hyperoxic conditions. These changes show that exposure of pseudoglandular lungs to hyperoxia modulates the lung architecture to resemble saccular lungs.

  9. Late appearance of a type I alveolar epithelial cell marker during fetal rat lung development.

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    Danto, S I; Zabski, S M; Crandall, E D

    1994-10-01

    Recent studies in fetal lung using immunological and molecular probes have revealed type I and type II cell phenotypic markers in primordial lung epithelial cells prior to the morphogenesis of these cell types. We have recently developed monoclonal antibodies specific for adult type I cells. To evaluate further the temporal appearance of the type I cell phenotype during alveolar epithelial cell ontogeny, we analyzed fetal lung development using one of our monoclonal antibodies (mAb VIII B2). The epitope recognized by mAb VIII B2 first appears in the canalicular stage of fetal lung development, at approx. embryonic day 19 (E19), in occasional, faintly stained tubules. Staining with this type I cell probe becomes more intense and more widespread with increasing gestational age, during which time the pattern of staining changes. Initially, all cells of the distal epithelial tubules are uniformly labelled along their apical and basolateral surfaces. As morphological differentiation of the alveolar epithelium proceeds, type I cell immunoreactivity appears to become restricted to the apical surface of the primitive type I cells in a pattern approaching that seen in the mature lung. We concurrently analyzed developing fetal lung with an antiserum to surfactant apoprotein-A (alpha-SP-A). Consistent with the findings of others, labeling of SP-A was first detectable in scattered cuboidal cells at E18. Careful examination of the double-labeled specimens suggested that some cells were reactive with both the VIII B2 and SP-A antibodies, particularly at E20. Confocal microscopic analysis of such sections from E20 lung confirmed this impression. Three populations of cells were detected: cells labeled only with alpha-SP-A, cells labeled only with mAb VIII B2, and a smaller subset of cells labeled by both.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Gene expression profile of androgen modulated genes in the murine fetal developing lung

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    Côté Mélissa

    2010-01-01

    Full Text Available Abstract Background Accumulating evidences suggest that sex affects lung development. Indeed, a higher incidence of respiratory distress syndrome is observed in male compared to female preterm neonates at comparable developmental stage and experimental studies demonstrated an androgen-related delay in male lung maturation. However, the precise mechanisms underlying these deleterious effects of androgens in lung maturation are only partially understood. Methods To build up a better understanding of the effect of androgens on lung development, we analyzed by microarrays the expression of genes showing a sexual difference and those modulated by androgens. Lungs of murine fetuses resulting from a timely mating window of 1 hour were studied at gestational day 17 (GD17 and GD18, corresponding to the period of surge of surfactant production. Using injections of the antiandrogen flutamide to pregnant mice, we hunted for genes in fetal lungs which are transcriptionally modulated by androgens. Results Results revealed that 1844 genes were expressed with a sexual difference at GD17 and 833 at GD18. Many genes were significantly modulated by flutamide: 1597 at GD17 and 1775 at GD18. Datasets were analyzed by using in silico tools for reconstruction of cellular pathways. Between GD17 and GD18, male lungs showed an intensive transcriptional activity of proliferative pathways along with the onset of lung differentiation. Among the genes showing a sex difference or an antiandrogen modulation of their expression, we specifically identified androgen receptor interacting genes, surfactant related genes in particularly those involved in the pathway leading to phospholipid synthesis, and several genes of lung development regulator pathways. Among these latter, some genes related to Shh, FGF, TGF-beta, BMP, and Wnt signaling are modulated by sex and/or antiandrogen treatment. Conclusion Our results show clearly that there is a real delay in lung maturation between

  11. Fetal lung development on MRI. Normal course and impairment due to premature rupture of membranes; Fetale Lungenentwicklung in der MRT. Normaler Verlauf und Beeintraechtigung durch vorzeitigen Blasensprung

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    Kasprian, G. [Medizinische Universitaet Wien (Austria). Klinik fuer Radiodiagnostik; Zentrum fuer Anatomie und Zellbiologie der Medizinischen Universitaet Wien (Austria). Arbeitsgruppe Integrative Morphologie; Brugger, P.C. [Zentrum fuer Anatomie und Zellbiologie der Medizinischen Universitaet Wien (Austria). Arbeitsgruppe Integrative Morphologie; Helmer, H.; Langer, M. [Medizinische Universitaet Wien (Austria). Klinik fuer Frauenheilkunde; Balassy, C.; Prayer, D. [Medizinische Universitaet Wien (Austria). Klinik fuer Radiodiagnostik

    2006-02-15

    A well-organized interplay between many molecular factors as well as mechanical forces influence fetal lung development. At the end of this complex process a sufficiently sized and structurally mature organ should ensure the postnatal survival of the newborn. Besides prenatal ultrasonography, magnetic resonance imaging (MRI) can now be used to investigate normal and pathological human lung growth in utero. Oligohydramnios, due to premature rupture of membranes (PROM), is an important risk factor for compromised fetal lung growth. In these situations MR volumetry can be used to measure the size of the fetal lung quite accurately. Together with the evaluation of lung signal intensities on T2-weighted sequences, fetuses with pulmonary hypoplasia can be readily detected. (orig.) [German] Die fetale Lungenentwicklung wird einerseits durch eine Vielzahl molekularer Faktoren und andererseits durch mechanisch-physiologische Kraefte beeinflusst. Ein geordnetes Zusammenspiel dieser Mechanismen fuehrt zu einem ausreichend grossen und strukturell reifen Organ, das sofort nach der Geburt das Ueberleben des Neugeborenen sicherstellt. Neben der praenatalen Ultraschalluntersuchung bietet nun auch die Magnetresonanztomographie (MRT) die Moeglichkeit, die normale und pathologische fetale Lungenentwicklung zu untersuchen. Ein wesentlicher Risikofaktor fuer eine Beeintraechtigung der Lungenentwicklung ist die verminderte Fruchtwassermenge nach vorzeitigem Blasensprung. In diesen Faellen kann die MR-Volumetrie dazu eingesetzt werden, die Groesse der fetalen Lungen relativ genau zu bestimmen. Gemeinsam mit der Beurteilung der MR-Signalintensitaeten des Lungengewebes auf T2-gewichteten Sequenzen koennen Feten mit hypoplastischen Lungen mit zunehmender Sicherheit bereits praenatal identifiziert werden. (orig.)

  12. Fetal lung development in the elephant reflects the adaptations required for snorkeling in adult life.

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    West, John B; Fu, Zhenxing; Gaeth, Ann P; Short, Roger V

    2003-11-14

    The adult elephant is unique among mammals in that the pleural membranes are thickened and the pleural cavity is obliterated by connective tissue. It has been suggested that this peculiar anatomy developed because the animal can snorkel at depth, and this behavior subjects the microvessels in the parietal pleura to a very large transmural pressure. To investigate the development of the parietal pleura, the thickness of the endothoracic fascia (ET) was measured in four fetal African elephants of approximate gestational age 111-130 days, and the appearances were compared with those in human, rabbit, rat and mouse fetuses of approximately the same stage of lung organogenesis. The mean thicknesses of ET in the elephant, human, rabbit, rat and mouse were 403, 53, 29, 27 and 37 microm, respectively. This very early development of a thick parietal pleura in the elephant fetus is consistent with the hypothesis of a long history of snorkeling in the elephant's putative aquatic ancestors.

  13. Structural Development, Cellular Differentiation and Proliferation of the Respiratory Epithelium in the Bovine Fetal Lung.

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    Drozdowska, J; Cousens, C; Finlayson, J; Collie, D; Dagleish, M P

    2016-01-01

    Fetal bovine lung samples of 11 different gestational ages were assigned to a classical developmental stage based on histological morphology. Immunohistochemistry was used to characterize the morphology of forming airways, proliferation rate of airway epithelium and the presence of epithelial cell types (i.e. ciliated cells, club cells, neuroepithelial cells (NECs) and type II pneumocytes). Typical structural organization of pseudoglandular (84-98 days gestational age [DGA]), canalicular (154-168 DGA) and alveolar (224-266 DGA) stages was recognized. In addition, transitional pseudoglandular-canalicular (112-126 DGA) and canalicular-saccular (182 DGA) morphologies were present. The embryonic stage was not observed. A significantly (P epithelium, on average 5.5% and 4.4% in bronchi and bronchioles, respectively, was present in the transitional pseudoglandular-canalicular phase (112-126 DGA) compared with all other phases, while from 8 weeks before term (224-266 DGA) proliferation had almost ceased. The first epithelial cells identified by specific marker proteins in the earliest samples available for study (84 DGA) were ciliated cells and NECs. Club cells were present initially at 112 DGA and type II pneumocytes at 224 DGA. At the latest time points (224-226 DGA) these latter cell types were still present at a much lower percentage compared with adult cattle. This study characterized bovine fetal lung development by histological morphology and cellular composition of the respiratory epithelium and suggests that the apparent structural anatomical maturity of the bovine lung at term is not matched by functional maturity of the respiratory epithelium.

  14. Fetal calcium regulates branching morphogenesis in the developing human and mouse lung: involvement of voltage-gated calcium channels.

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    Brennan, Sarah C; Finney, Brenda A; Lazarou, Maria; Rosser, Anne E; Scherf, Caroline; Adriaensen, Dirk; Kemp, Paul J; Riccardi, Daniela

    2013-01-01

    Airway branching morphogenesis in utero is essential for optimal postnatal lung function. In the fetus, branching morphogenesis occurs during the pseudoglandular stage (weeks 9-17 of human gestation, embryonic days (E)11.5-16.5 in mouse) in a hypercalcaemic environment (~1.7 in the fetus vs. ~1.1-1.3 mM for an adult). Previously we have shown that fetal hypercalcemia exerts an inhibitory brake on branching morphogenesis via the calcium-sensing receptor. In addition, earlier studies have shown that nifedipine, a selective blocker of L-type voltage-gated Ca(2+) channels (VGCC), inhibits fetal lung growth, suggesting a role for VGCC in lung development. The aim of this work was to investigate the expression of VGCC in the pseudoglandular human and mouse lung, and their role in branching morphogenesis. Expression of L-type (CaV1.2 and CaV1.3), P/Q type (CaV2.1), N-type (CaV2.2), R-type (CaV2.3), and T-type (CaV3.2 and CaV3.3) VGCC was investigated in paraffin sections from week 9 human fetal lungs and E12.5 mouse embryos. Here we show, for the first time, that Cav1.2 and Cav1.3 are expressed in both the smooth muscle and epithelium of the developing human and mouse lung. Additionally, Cav2.3 was expressed in the lung epithelium of both species. Incubating E12.5 mouse lung rudiments in the presence of nifedipine doubled the amount of branching, an effect which was partly mimicked by the Cav2.3 inhibitor, SNX-482. Direct measurements of changes in epithelial cell membrane potential, using the voltage-sensitive fluorescent dye DiSBAC2(3), demonstrated that cyclic depolarisations occur within the developing epithelium and coincide with rhythmic occlusions of the lumen, driven by the naturally occurring airway peristalsis. We conclude that VGCC are expressed and functional in the fetal human and mouse lung, where they play a role in branching morphogenesis. Furthermore, rhythmic epithelial depolarisations evoked by airway peristalsis would allow for branching to match

  15. Fetal calcium regulates branching morphogenesis in the developing human and mouse lung: involvement of voltage-gated calcium channels.

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    Sarah C Brennan

    Full Text Available Airway branching morphogenesis in utero is essential for optimal postnatal lung function. In the fetus, branching morphogenesis occurs during the pseudoglandular stage (weeks 9-17 of human gestation, embryonic days (E11.5-16.5 in mouse in a hypercalcaemic environment (~1.7 in the fetus vs. ~1.1-1.3 mM for an adult. Previously we have shown that fetal hypercalcemia exerts an inhibitory brake on branching morphogenesis via the calcium-sensing receptor. In addition, earlier studies have shown that nifedipine, a selective blocker of L-type voltage-gated Ca(2+ channels (VGCC, inhibits fetal lung growth, suggesting a role for VGCC in lung development. The aim of this work was to investigate the expression of VGCC in the pseudoglandular human and mouse lung, and their role in branching morphogenesis. Expression of L-type (CaV1.2 and CaV1.3, P/Q type (CaV2.1, N-type (CaV2.2, R-type (CaV2.3, and T-type (CaV3.2 and CaV3.3 VGCC was investigated in paraffin sections from week 9 human fetal lungs and E12.5 mouse embryos. Here we show, for the first time, that Cav1.2 and Cav1.3 are expressed in both the smooth muscle and epithelium of the developing human and mouse lung. Additionally, Cav2.3 was expressed in the lung epithelium of both species. Incubating E12.5 mouse lung rudiments in the presence of nifedipine doubled the amount of branching, an effect which was partly mimicked by the Cav2.3 inhibitor, SNX-482. Direct measurements of changes in epithelial cell membrane potential, using the voltage-sensitive fluorescent dye DiSBAC2(3, demonstrated that cyclic depolarisations occur within the developing epithelium and coincide with rhythmic occlusions of the lumen, driven by the naturally occurring airway peristalsis. We conclude that VGCC are expressed and functional in the fetal human and mouse lung, where they play a role in branching morphogenesis. Furthermore, rhythmic epithelial depolarisations evoked by airway peristalsis would allow for branching to

  16. Changes in Maternal Glucose Metabolism after the Administration of Dexamethasone for Fetal Lung Development

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    Xu Jian Yun

    2012-01-01

    Methods. Singleton pregnancies, twin pregnancies, and pregnancies with IGT between 28 and 33 weeks of gestation whose mothers were treated with dexamethasone were enrolled in this study. Exclusion criteria included gestational hypertension, diabetes, renal disorders, and infectious diseases. The fasting plasma glucose and insulin levels were checked before administration and 24 h, 48 h, and 72 h after treatment was completed. Results. Mean glucose levels were significantly higher in the twin pregnancy and IGT groups at 24 h and 48 h after the administration of dexamethasone than those in the singleton pregnancy group (P<0.05. Although there was no significant difference in glucose levels before administration and 72 h after dexamethasone administration among the three groups, insulin levels in the IGT group were significantly higher (P<0.05. Insulin levels in the singleton pregnancy group at 24 h and 48 h after treatment were significantly lower than in the twin and IGT groups. Conclusion. The effects on maternal fasting blood glucose and insulin levels of dexamethasone administrated to promote fetal lung maturation correlated with embryo number and the presence of IGT.

  17. Fetal development

    Science.gov (United States)

    ... begins to move and stretch. The liver and pancreas produce secretions. Your little one now makes sucking ... The baby is more active with increased muscle development. The mother can feel the baby moving. Baby's ...

  18. Changing patterns of fetal lung maturity testing

    National Research Council Canada - National Science Library

    McGinnis, K T; Brown, J A; Morrison, J C

    2008-01-01

    In our laboratory, a decrease in fetal lung maturity (FLM) testing on amniotic fluid occurred over a 10-year period, and we desired to determine if this was a national phenomenon and, if present, ascertain possible etiologies...

  19. Magnetic resonance imaging of the fetal lung: a pictorial essay

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    Cannie, M.; Keyzer, F. de; Kerkhove, F. van; Meersschaert, J. [University Hospitals Leuven, Department of Radiology, Leuven (Belgium); Jani, J.; Lewi, L.; Deprest, J. [University Hospitals Leuven, Department Obstetrics and Gynaecology, Leuven (Belgium); Dymarkowski, S. [University Hospitals Leuven, Department of Radiology, Leuven (Belgium); UZ Gasthuisberg, Department of Radiology, Leuven (Belgium)

    2008-07-15

    Ultrasound, which is now a widely available and generally accepted, low-cost technique with real-time properties, is the screening investigation of choice in fetal medicine. However, enthusiasm for fetal prenatal magnetic resonance imaging (MRI) is rising, because of the absence of known biological risks, the increasing ease of performing of fetal MRI and the superb contrast resolution provided. Over the last 10 years, the technology has advanced dramatically. Fast imaging sequences have allowed better MRI visualization of the unborn patient than ever before. As a consequence, experience with fetal MRI is gradually expanding. We are beginning to appreciate the clinical conditions where fetal MRI can complement the ultrasound findings. Apart from the central nervous system, MRI of the fetal lung has received the most attention. Fetal MRI can be used to assess thoracic structural anomalies, lung development as well as maturation. The introduction of fetal therapy for severe lung hypoplasia, associated with congenital diaphragmatic hernia (CDH), has recently boosted the application. This review aims to highlight MRI techniques used to image the lungs of the unborn child and to point out their strengths and limitations in specific conditions. (orig.)

  20. Pre- and Postnatal Lung Development, Maturation, and Plasticity: Leptin mediates the parathyroid hormone-related protein paracrine stimulation of fetal lung maturation

    National Research Council Canada - National Science Library

    Torday, J. S; Sun, H; Wang, L; Torres, E

    2002-01-01

    ... express leptin beginning on embryonic day (E) 17, increasing 7- to 10-fold by E20. Leptin and its receptor are expressed mutually exclusively by fetal lung fibroblasts and type II cells, suggesting a paracrine signaling "loop...

  1. Assessment of lung development in isolated congenital diaphragmatic hernia using signal intensity ratios on fetal MR imaging.

    Science.gov (United States)

    Balassy, Csilla; Kasprian, Gregor; Brugger, Peter C; Weber, Michael; Csapo, Bence; Herold, Christian; Prayer, Daniela

    2010-04-01

    To investigate developmental changes in the apparently unaffected contralateral lung by using signal intensity ratios (SIR) and lung volumes (LV), and to search for correlation with clinical outcome. Twenty-five fetuses (22-37 weeks' gestation) were examined. Lung/liver signal intensity ratios (LLSIR) were assessed on T1-weighted and T2-weighted sequences for both lungs, then together with LV compared with age-matched controls of 91 fetuses by using the U test. Differences in LLSIRs and lung volumes were correlated with neonatal outcomes. LLSIRs in fetuses with congenital diaphragmatic hernia (CDH) were significantly higher in both lungs on T1-weighted images and significantly lower on T2-weighted images, compared with normals (p < 0.05), increasing on T2-weighted imaging and decreasing on T1-weighted imaging during gestation. Total LV were significantly smaller in the CDH group than in controls (p < 0.05). No significant differences in LLSIR of the two lungs were found. Outcomes correlated significantly with total LV, but not with LLSIR. Changes in LLSIR seem to reflect developmental impairment in CDH; however, they provide no additional information in predicting outcome. LV remains the best indicator on fetal MR imaging of neonatal survival in isolated, left-sided CDH.

  2. Assessment of lung development in isolated congenital diaphragmatic hernia using signal intensity ratios on fetal MR imaging

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    Balassy, Csilla; Kasprian, Gregor; Weber, Michael; Herold, Christian; Prayer, Daniela [Medical University of Vienna, Department of Radiology, Vienna (Austria); Brugger, Peter C. [Medical University of Vienna, Centre of Anatomy and Cell Biology, Vienna (Austria); Csapo, Bence [Medical University of Vienna, Department of Obstetrics and Gyneocology, Vienna (Austria)

    2010-04-15

    To investigate developmental changes in the apparently unaffected contralateral lung by using signal intensity ratios (SIR) and lung volumes (LV), and to search for correlation with clinical outcome. Twenty-five fetuses (22-37 weeks' gestation) were examined. Lung/liver signal intensity ratios (LLSIR) were assessed on T1-weighted and T2-weighted sequences for both lungs, then together with LV compared with age-matched controls of 91 fetuses by using the U test. Differences in LLSIRs and lung volumes were correlated with neonatal outcomes. LLSIRs in fetuses with congenital diaphragmatic hernia (CDH) were significantly higher in both lungs on T1-weighted images and significantly lower on T2-weighted images, compared with normals (p < 0.05), increasing on T2-weighted imaging and decreasing on T1-weighted imaging during gestation. Total LV were significantly smaller in the CDH group than in controls (p < 0.05). No significant differences in LLSIR of the two lungs were found. Outcomes correlated significantly with total LV, but not with LLSIR. Changes in LLSIR seem to reflect developmental impairment in CDH; however, they provide no additional information in predicting outcome. LV remains the best indicator on fetal MR imaging of neonatal survival in isolated, left-sided CDH. (orig.)

  3. Diffusion-weighted MR imaging of the normal fetal lung

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    Balassy, Csilla; Kasprian, Gregor; Weber, Michael; Hoermann, Marcus; Bankier, Alexander; Herold, Christian J.; Prayer, Daniela [Medical University of Vienna, Department of Radiology, Vienna (Austria); Brugger, Peter C. [Medical University of Vienna, Center of Anatomy and Cell Biology, Vienna (Austria); Csapo, Bence [Medical University of Vienna, Department of Obstetrics and Gyneocology, Vienna (Austria); Bammer, Roland [University of Stanford, Department of Radiology, Stanford, CA (United States)

    2008-04-15

    To quantify apparent diffusion coefficient (ADC) changes in fetuses with normal lungs and to determine whether ADC can be used in the assessment of fetal lung development. In 53 pregnancies (20-37th weeks of gestation), we measured ADC on diffusion-weighted imaging (DWI) in the apical, middle, and basal thirds of the right lung. ADCs were correlated with gestational age. Differences between the ADCs were assessed. Fetal lung volumes were measured on T2-weighted sequences and correlated with ADCs and with age. ADCs were 2.13 {+-} 0.44 {mu}m{sup 2}/ms (mean {+-} SD) in the apex, 1.99 {+-} 0.42 {mu}m{sup 2}/ms (mean {+-} SD) in the middle third, and 1.91 {+-} 0.41 {mu}m{sup 2}/ms (mean {+-} SD) in the lung base. Neither the individual ADC values nor average ADC values showed a significant correlation with gestational age or with lung volumes. Average ADCs decreased significantly from the lung apex toward the base. Individual ADCs showed little absolute change and heterogeneity. Lung volumes increased significantly during gestation. We have not been able to identify a pattern of changes in the ADC values that correlate with lung maturation. Furthermore, the individual, gravity-related ADC changes are subject to substantial variability and show nonuniform behavior. ADC can therefore not be used as an indicator of lung maturity. (orig.)

  4. Diffusion-weighted MR imaging of the normal fetal lung.

    Science.gov (United States)

    Balassy, Csilla; Kasprian, Gregor; Brugger, Peter C; Csapo, Bence; Weber, Michael; Hörmann, Marcus; Bankier, Alexander; Bammer, Roland; Herold, Christian J; Prayer, Daniela

    2008-04-01

    To quantify apparent diffusion coefficient (ADC) changes in fetuses with normal lungs and to determine whether ADC can be used in the assessment of fetal lung development. In 53 pregnancies (20-37th weeks of gestation), we measured ADC on diffusion-weighted imaging (DWI) in the apical, middle, and basal thirds of the right lung. ADCs were correlated with gestational age. Differences between the ADCs were assessed. Fetal lung volumes were measured on T2-weighted sequences and correlated with ADCs and with age. ADCs were 2.13 +/- 0.44 microm(2)/ms (mean +/- SD) in the apex, 1.99 +/- 0.42 microm(2)/ms (mean +/- SD) in the middle third, and 1.91 +/- 0.41 microm(2)/ms (mean +/- SD) in the lung base. Neither the individual ADC values nor average ADC values showed a significant correlation with gestational age or with lung volumes. Average ADCs decreased significantly from the lung apex toward the base. Individual ADCs showed little absolute change and heterogeneity. Lung volumes increased significantly during gestation. We have not been able to identify a pattern of changes in the ADC values that correlate with lung maturation. Furthermore, the individual, gravity-related ADC changes are subject to substantial variability and show nonuniform behavior. ADC can therefore not be used as an indicator of lung maturity.

  5. Fetal cardiac disease and fetal lung volume: an in utero MRI investigation.

    Science.gov (United States)

    Mlczoch, Elisabeth; Schmidt, Lisa; Schmid, Maximilian; Kasprian, Gregor; Frantal, Sophie; Berger-Kulemann, Vanessa; Prayer, Daniela; Michel-Behnke, Ina; Salzer-Muhar, Ulrike

    2014-03-01

    Magnetic resonance imaging (MRI) is a powerful, noninvasive tool to study fetal lung volumes after 18 weeks of gestation in vivo. In neonates with congenital heart disease (CHD), proper lung function is essential for postnatal survival. Antenatal detection of abnormal pulmonary development may help to optimize prenatal and perinatal management of at-risk fetuses. We aimed to investigate lung volumes in fetuses with prenatally diagnosed heart disease. A cross-sectional, retrospective study of 105 consecutive singleton pregnancies with CHD and a control, non-CHD group (n = 115), that underwent fetal MRI was performed. The heart defects detected were divided into four groups. Lung volumes of fetuses with heart disease were compared with control, non-CHD fetuses. In addition, z-scores of lung volumes were calculated for the CHD group (normal range z-scores from -2-+2). As a group, fetuses with CHD have significantly smaller lung volumes compared with control fetuses when corrected by gestational age (GA) (p = 0.049). Of the 105 CHD fetuses studied, 18 had lung volumes with a z-score < -2. Fetuses with different types of CHD showed similar lung volumes. Our data indicate that postpartum pulmonary symptoms and outcome in neonates with congenital heart disease may be attributed to the cardiac disease itself and in part to smaller lung volumes. © 2013 John Wiley & Sons, Ltd.

  6. Choriodecidual infection downregulates angiogenesis and morphogenesis pathways in fetal lungs from Macaca nemestrina.

    Directory of Open Access Journals (Sweden)

    Ryan M McAdams

    Full Text Available BACKGROUND: Intrauterine exposure to amniotic fluid (AF cytokines is thought to predispose to bronchopulmonary dysplasia (BPD. We evaluated the effects of GBS exposure on RNA expression in fetal lung tissue to determine early molecular pathways associated with fetal lung injury that may progress to BPD. METHODS: Ten chronically catheterized pregnant monkeys (Macaca nemestrina at 118-125 days gestation (term = 172 days received choriodecidual inoculation of either: 1 Group B Streptococcus (n = 5 or 2 saline (n = 5. Cesarean section and fetal necropsy was performed in the first week after GBS or saline inoculation regardless of labor. RNA was extracted from fetal lungs and profiled by microarray. Results were analyzed using single gene, Gene Set, and Ingenuity Pathway Analysis. Validation was by RT-PCR and immunohistochemistry. RESULTS: Despite uterine quiescence in most cases, fetal lung injury occurred in four GBS cases (intra-alveolar neutrophils, interstitial thickening and one control (peri-mortem hemorrhage. Significant elevations of AF cytokines (TNF-α, IL-8, IL-1β, IL-6 were detected in GBS versus controls (p<0.05. Lung injury was not directly caused by GBS, because GBS was undetectable by culture and PCR in the AF and fetal lungs. A total of 335 genes were differentially expressed greater than 1.5 fold (p<0.05 with GBS exposure associated with a striking upregulation of genes in innate and adaptive immunity and downregulation of pathways for angiogenesis, morphogenesis, and cellular growth and development. CONCLUSIONS: A transient choriodecidual infection may induce fetal lung injury with profound alterations in the genetic program of the fetal lung before signs of preterm labor. Our results provide a window for the first time into early molecular pathways disrupting fetal lung angiogenesis and morphogenesis before preterm labor occurs, which may set the stage for BPD. A strategy to prevent BPD should target the fetus in

  7. Developmental Expression and Glucocorticoid Control of the Leptin Receptor in Fetal Ovine Lung.

    Science.gov (United States)

    De Blasio, Miles J; Boije, Maria; Vaughan, Owen R; Bernstein, Brett S; Davies, Katie L; Plein, Alice; Kempster, Sarah L; Smith, Gordon C S; Charnock-Jones, D Stephen; Blache, Dominique; Wooding, F B Peter; Giussani, Dino A; Fowden, Abigail L; Forhead, Alison J

    2015-01-01

    The effects of endogenous and synthetic glucocorticoids on fetal lung maturation are well-established, although the role of leptin in lung development before birth is unclear. This study examined mRNA and protein levels of the signalling long-form leptin receptor (Ob-Rb) in fetal ovine lungs towards term, and after experimental manipulation of glucocorticoid levels in utero by fetal cortisol infusion or maternal dexamethasone treatment. In fetal ovine lungs, Ob-Rb protein was localised to bronchiolar epithelium, bronchial cartilage, vascular endothelium, alveolar macrophages and type II pneumocytes. Pulmonary Ob-Rb mRNA abundance increased between 100 (0.69 fractional gestational age) and 144 days (0.99) of gestation, and by 2-4-fold in response to fetal cortisol infusion and maternal dexamethasone treatment. In contrast, pulmonary Ob-Rb protein levels decreased near term and were halved by glucocorticoid treatment, without any significant change in phosphorylated signal transducer and activator of transcription-3 (pSTAT3) at Ser727, total STAT3 or the pulmonary pSTAT3:STAT3 ratio. Leptin mRNA was undetectable in fetal ovine lungs at the gestational ages studied. These findings demonstrate differential control of pulmonary Ob-Rb transcript abundance and protein translation, and/or post-translational processing, by glucocorticoids in utero. Localisation of Ob-Rb in the fetal ovine lungs, including alveolar type II pneumocytes, suggests a role for leptin signalling in the control of lung growth and maturation before birth.

  8. Morphological effects of chronic bilateral phrenectomy or vagotomy in the fetal lamb lung.

    Science.gov (United States)

    Alcorn, D; Adamson, T M; Maloney, J E; Robinson, P M

    1980-06-01

    The relationship between fetal espiratory activity and fetal lung development has been studied at the cellular level using two experimental models. Chronic bilateral phrenectomy over a period of 20-28 days during the last trimester of the fetal lamb resulted in hypoplastic lungs, although cellular maturity, as indicated by the presence of alveolar epithelial Type II cells, was present. In the lungs from fetal lambs undergoing sham operations for a similar time course there was evidence of enhanced alveolar proliferation when compared with lungs from normal fetal sheep of a similar gastational age, most probably as a result of operative stress. Following chronic bilateral vagotomy no changes in size or histology of the fetal lamb lungs were detected. At an ultrastructural level, however, inclusions of Type II cells consistently showed the loss of the typical osmiophilic lamellated appearance. These results indicate the importance of the fetal breathing apparatus in maintaining a volume of lung liquid which is adequate for normal pulmonary development, particularly during the phase in which alveoli are formed.

  9. Fetal Health and Development

    Science.gov (United States)

    ... specific prenatal tests to monitor both the mother's health and fetal health during each trimester. With modern technology, health professionals can Detect birth defects Identify problems that ...

  10. Mechanotransduction via TRPV4 regulates inflammation and differentiation in fetal mouse distal lung epithelial cells.

    Science.gov (United States)

    Nayak, Pritha S; Wang, Yulian; Najrana, Tanbir; Priolo, Lauren M; Rios, Mayra; Shaw, Sunil K; Sanchez-Esteban, Juan

    2015-05-27

    Mechanical ventilation plays a central role in the injury of premature lungs. However, the mechanisms by which mechanical signals trigger an inflammatory cascade to promote lung injury are not well-characterized. Transient receptor potential vanilloid 4 (TRPV4), a calcium-permeable mechanoreceptor channel has been shown to be a major determinant of ventilator-induced acute lung injury in adult models. However, the role of these channels as modulators of inflammation in immature lungs is unknown. In this study, we tested the hypothesis that TRPV4 channels are important mechanotransducers in fetal lung injury. Expression of TRPV4 in the mouse fetal lung was investigated by immunohistochemistry, Western blot and qRT-PCR. Isolated fetal epithelial cells were exposed to mechanical stimulation using the Flexcell Strain Unit and inflammation and differentiation were analyzed by ELISA and SP-C mRNA, respectively. TRPV4 is developmentally regulated in the fetal mouse lung; it is expressed in the lung epithelium and increases with advanced gestation. In contrast, in isolated epithelial cells, TRPV4 expression is maximal at E17-E18 of gestation. Mechanical stretch increases TRPV4 in isolated fetal epithelial cells only during the canalicular stage of lung development. Using the TRPV4 agonist GSK1016790A, the antagonist HC-067047, and the cytokine IL-6 as a marker of inflammation, we observed that TRPV4 regulates release of IL-6 via p38 and ERK pathways. Interestingly, stretch-induced differentiation of fetal epithelial cells was also modulated by TRPV4. These studies demonstrate that TRPV4 may play an important role in the transduction of mechanical signals in the fetal lung epithelium by modulating not only inflammation but also the differentiation of fetal epithelial cells.

  11. Contribution of Fetal, but Not Adult, Pulmonary Mesothelium to Mesenchymal Lineages in Lung Homeostasis and Fibrosis.

    Science.gov (United States)

    von Gise, Alexander; Stevens, Sean M; Honor, Leah B; Oh, Jin Hee; Gao, Chi; Zhou, Bin; Pu, William T

    2016-02-01

    The lung is enveloped by a layer of specialized epithelium, the pulmonary mesothelium. In other organs, mesothelial cells undergo epithelial-mesenchymal transition and contribute to organ stromal cells. The contribution of pulmonary mesothelial cells (PMCs) to the developing lung has been evaluated with differing conclusions. PMCs have also been indirectly implicated in lung fibrosis in the progressive, fatal lung disease idiopathic pulmonary fibrosis. We used fetal or postnatal genetic pulse labeling of PMCs to assess their fate in murine development, normal lung homeostasis, and models of pulmonary fibrosis. We found that most fetal PMC-derived mesenchymal cells (PMCDCs) expressed markers of pericytes and fibroblasts, only a small minority expressed smooth muscle markers, and none expressed endothelial cell markers. Postnatal PMCs did not contribute to lung mesenchyme during normal lung homeostasis or in models of lung fibrosis. However, fetal PMCDCs were abundant and actively proliferating within fibrotic regions in lung fibrosis models, suggesting that they actively participate in the fibrotic process. These data clarify the role of fetal and postnatal PMCDCs in lung development and disease.

  12. IL-1β expression in the distal lung epithelium disrupts lung morphogenesis and epithelial cell differentiation in fetal mice.

    Science.gov (United States)

    Hogmalm, Anna; Bry, Maija; Strandvik, Birgitta; Bry, Kristina

    2014-01-01

    Perinatal inflammation and the inflammatory cytokine IL-1 can modify lung morphogenesis. To examine the effects of antenatal expression of IL-1β in the distal airway epithelium on fetal lung morphogenesis, we studied lung development and surfactant expression in fetal mice expressing human IL-1β under the control of the surfactant protein (SP)-C promoter. IL-1β-expressing pups suffered respiratory failure and died shortly after birth. IL-1β caused fetal lung inflammation and enhanced the expression of keratinocyte-derived chemokine (KC/CXCL1) and monocyte chemoattractant protein 3 (MCP-3/CCL7), the calgranulins S100A8 and S100A9, the acute-phase protein serum amyloid A3, the chitinase-like proteins Ym1 and Ym2, and pendrin. IL-1β decreased the percentage of the total distal lung area made up of air saccules and the number of air saccules in the lungs of fetal mice. IL-1β inhibited the expression of VEGF-A and its receptors VEGFR-1 and VEGFR-2. The percentage of the cellular area of the distal lung made up of capillaries was decreased in IL-1β-expressing fetal mice. IL-1β suppressed the production of SP-B and pro-SP-C and decreased the amount of phosphatidylcholine and the percentage of palmitic acid in the phosphatidylcholine fraction of lung phospholipids, indicating that IL-1β prevented the differentiation of type II epithelial cells. The production of Clara cell secretory protein in the nonciliated bronchiolar (Clara) cells was likewise suppressed by IL-1β. In conclusion, expression of IL-1β in the epithelium of the distal airways disrupted the development of the airspaces and capillaries in the fetal lung and caused fatal respiratory failure at birth.

  13. Maternal Baicalin Treatment Increases Fetal Lung Surfactant Phospholipids in Rats

    Directory of Open Access Journals (Sweden)

    Chung-Ming Chen

    2011-01-01

    Full Text Available Baicalin is a flavonoid compound purified from the medicinal plant Scutellaria baicalensis Georgi and has been reported to stimulate surfactant protein (SP-A gene expression in human lung epithelial cell lines (H441. The aims of this study were to determine whether maternal baicalin treatment could increase lung surfactant production and induce lung maturation in fetal rats. This study was performed with timed pregnant Sprague-Dawley rats. One-day baicalin group mothers were injected intraperitoneally with baicalin (5 mg/kg/day on Day 18 of gestation. Two-day baicalin group mothers were injected intraperitoneally with baicalin (5 mg/kg/day on Days 17 and 18 of gestation. Control group mothers were injected with vehicle alone on Day 18 of gestation. On Day 19 of gestation, fetuses were delivered by cesarean section. Maternal treatment with 2-day baicalin significantly increased saturated phospholipid when compared with control group and total phospholipid in fetal lung tissue when compared with control and 1-day baicalin groups. Antenatal treatment with 2-day baicalin significantly increased maternal growth hormone when compared with control group. Fetal lung SP-A mRNA expression and maternal serum corticosterone levels were comparable among the three experimental groups. Maternal baicalin treatment increases pulmonary surfactant phospholipids of fetal rat lungs and the improvement was associated with increased maternal serum growth hormone. These results suggest that antenatal baicalin treatment might accelerate fetal rat lung maturation.

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  5. Endotoxin-induced maturation of monocytes in preterm fetal sheep lung.

    Science.gov (United States)

    Kramer, Boris W; Joshi, Shubhada N; Moss, Timothy J M; Newnham, John P; Sindelar, Richard; Jobe, Alan H; Kallapur, Suhas G

    2007-08-01

    The fetal lung normally contains immature monocytes and very few mature macrophages. The chorioamnionitis frequently associated with preterm birth induces monocyte influx into the fetal lung. Previous studies demonstrated that monocytes in the developing lung can mediate lung injury responses that resemble BPD in humans. We hypothesized that chorioamnionitis would induce maturation of immature monocytes in the fetal lung. Groups of three to seven time-mated ewes received saline or 10 mg of endotoxin (Escherichia coli 055:B5) in saline by intra-amniotic injection for intervals from 1 to 14 days before operative delivery at 124 days of gestational age. Monocytic cells from lung tissue were recovered using Percoll gradients. Monocytic cells consistent with macrophages were identified morphologically and by myosin heavy chain class II expression. An increase in macrophages was preceded by induction of granulocyte-macrophage colony-stimulating factor in the lung and subsequent activation of the transcription factor PU.1. The production of IL-6 by monocytes/macrophages in response to endotoxin challenge in vitro increased 7 and 14 days after exposure to intra-amniotic endotoxin. Recombinant TNF-alpha induced IL-6 production by lung monocytic cells exposed to intra-amniotic endotoxin but not in control cells. Monocytic phagocytosis of apoptotic neutrophils also increased 7 and 14 days after exposure to intra-amniotic endotoxin. Intra-amniotic endotoxin induced lung monocytes to develop into functionally mature cells consistent with macrophages. These findings have implications for lung immune responses after exposure to chorioamnionitis.

  6. Developmental Expression and Glucocorticoid Control of the Leptin Receptor in Fetal Ovine Lung.

    Directory of Open Access Journals (Sweden)

    Miles J De Blasio

    Full Text Available The effects of endogenous and synthetic glucocorticoids on fetal lung maturation are well-established, although the role of leptin in lung development before birth is unclear. This study examined mRNA and protein levels of the signalling long-form leptin receptor (Ob-Rb in fetal ovine lungs towards term, and after experimental manipulation of glucocorticoid levels in utero by fetal cortisol infusion or maternal dexamethasone treatment. In fetal ovine lungs, Ob-Rb protein was localised to bronchiolar epithelium, bronchial cartilage, vascular endothelium, alveolar macrophages and type II pneumocytes. Pulmonary Ob-Rb mRNA abundance increased between 100 (0.69 fractional gestational age and 144 days (0.99 of gestation, and by 2-4-fold in response to fetal cortisol infusion and maternal dexamethasone treatment. In contrast, pulmonary Ob-Rb protein levels decreased near term and were halved by glucocorticoid treatment, without any significant change in phosphorylated signal transducer and activator of transcription-3 (pSTAT3 at Ser727, total STAT3 or the pulmonary pSTAT3:STAT3 ratio. Leptin mRNA was undetectable in fetal ovine lungs at the gestational ages studied. These findings demonstrate differential control of pulmonary Ob-Rb transcript abundance and protein translation, and/or post-translational processing, by glucocorticoids in utero. Localisation of Ob-Rb in the fetal ovine lungs, including alveolar type II pneumocytes, suggests a role for leptin signalling in the control of lung growth and maturation before birth.

  7. Prenatal diagnosis of fetal lung maturity by magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Itoh, Hitoshi; Kakizaki, Dai; Nagai, Atsushi; Akutagawa, Osamu; Itokazu, Isao; Iso, Kazuo; Abe, Kimihiko; Takayama, Masaomi [Tokyo Medical Coll. (Japan); Nohira, Tomoyoshi [Tokyo Medical Coll. (Japan). Hachioji Medical Center

    2003-04-01

    The objective of this study was to evaluate the usefulness of magnetic resonance imaging (MRI) for prenatal diagnosis of fetal lung maturity. The subjects comprised 28 singleton fetuses, and underwent MRI in the third trimester (32.71{+-}3.00 wks). After obtaining axial and coronal scout images of the whole pelvis, we obtained a transverse image, a coronal image and a sagittal image of fetuses with a half-Fourier acquisition single-shot turbo-spin-echo (HASTE) sequence, determined the intensity level of the fetal lung (right lung intensity level: RL, left lung intensity level: LL). The intensity level of background outside of the maternal body was obtained as the control intensity level (CL). The contrast value (CV) of each fetal lung was calculated by the numerical formula; CV=(RL or LL-CL)/CL. We evaluated the changes of CV during the third trimester and relationship between CV and gestational weeks. There was no significant correlation between gestational weeks and RL (P=.3887), LL (P=.2367). There was a significant increase in both right and left CV (RCV=(RL-CL)/CL: P=.0108, LCV=(LL-CL)/CL: P=.0165) with gestational age. It was suggested that the fetal lung maturation could be diagnosed with HASTE using the CV formula. (author)

  8. Local Fetal Lung Renin-Angiotensin System as a Target to Treat Congenital Diaphragmatic Hernia

    Science.gov (United States)

    Nogueira-Silva, Cristina; Carvalho-Dias, Emanuel; Piairo, Paulina; Nunes, Susana; Baptista, Maria J; Moura, Rute S; Correia-Pinto, Jorge

    2012-01-01

    Antenatal stimulation of lung growth is a reasonable approach to treat congenital diaphragmatic hernia (CDH), a disease characterized by pulmonary hypoplasia and hypertension. Several evidences from the literature demonstrated a possible involvement of renin-angiotensin system (RAS) during fetal lung development. Thus, the expression pattern of renin, angiotensin-converting enzyme, angiotensinogen, type 1 (AT1) and type 2 (AT2) receptors of angiotensin II (ANGII) was assessed by immunohisto-chemistry throughout gestation, whereas the function of RAS in the fetal lung was evaluated using fetal rat lung explants. These were morphometrically analyzed and intracellular pathway alterations assessed by Western blot. In nitrofen-induced CDH model, pregnant rats were treated with saline or PD-123319. In pups, lung growth, protein/DNA ratio, radial saccular count, epithelial differentiation and lung maturation, vascular morphometry, right ventricular hypertrophy and overload molecular markers, gasometry and survival time were evaluated. Results demonstrated that all RAS components were constitutively expressed in the lung during gestation and that ANGII had a stimulatory effect on lung branching, mediated by AT1 receptor, through p44/42 and Akt phosphorylation. This stimulatory effect on lung growth was mimicked by AT2-antagonist (PD-123319) treatment. In vivo antenatal PD-123319 treatment increased lung growth, ameliorated indirect parameters of pulmonary hypertension, improved lung function and survival time in nonventilated CDH pups, without maternal or fetal deleterious effects. Therefore, this study demonstrated a local and physiologically active RAS during lung morphogenesis. Moreover, selective inhibition of AT2 receptor is presented as a putative antenatal therapy for CDH. PMID:22113494

  9. Local fetal lung renin-angiotensin system as a target to treat congenital diaphragmatic hernia.

    Science.gov (United States)

    Nogueira-Silva, Cristina; Carvalho-Dias, Emanuel; Piairo, Paulina; Nunes, Susana; Baptista, Maria J; Moura, Rute S; Correia-Pinto, Jorge

    2012-03-27

    Antenatal stimulation of lung growth is a reasonable approach to treat congenital diaphragmatic hernia (CDH), a disease characterized by pulmonary hypoplasia and hypertension. Several evidences from the literature demonstrated a possible involvement of renin-angiotensin system (RAS) during fetal lung development. Thus, the expression pattern of renin, angiotensin-converting enzyme, angiotensinogen, type 1 (AT₁) and type 2 (AT₂) receptors of angiotensin II (ANGII) was assessed by immunohisto-chemistry throughout gestation, whereas the function of RAS in the fetal lung was evaluated using fetal rat lung explants. These were morphometrically analyzed and intracellular pathway alterations assessed by Western blot. In nitrofen-induced CDH model, pregnant rats were treated with saline or PD-123319. In pups, lung growth, protein/DNA ratio, radial saccular count, epithelial differentiation and lung maturation, vascular morphometry, right ventricular hypertrophy and overload molecular markers, gasometry and survival time were evaluated. Results demonstrated that all RAS components were constitutively expressed in the lung during gestation and that ANGII had a stimulatory effect on lung branching, mediated by AT₁ receptor, through p44/42 and Akt phosphorylation. This stimulatory effect on lung growth was mimicked by AT₂-antagonist (PD-123319) treatment. In vivo antenatal PD-123319 treatment increased lung growth, ameliorated indirect parameters of pulmonary hypertension, improved lung function and survival time in nonventilated CDH pups, without maternal or fetal deleterious effects. Therefore, this study demonstrated a local and physiologically active RAS during lung morphogenesis. Moreover, selective inhibition of AT₂ receptor is presented as a putative antenatal therapy for CDH.

  10. The impact of vitamin D on fetal and neonatal lung maturation

    DEFF Research Database (Denmark)

    Lykkedegn, Sine; Sorensen, Grith Lykke; Beck-Nielsen, Signe Sparre

    2015-01-01

    Med, Embase and Cochrane databases with the terms vitamin D AND (surfactant OR lung maturation OR lung development OR respiratory distress syndrome OR fetal lung OR prematurity OR bronchopulmonary dysplasia). Three human studies, ten animal studies, two laboratory studies and one combined animal......Respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) are major complications to preterm birth. Hypovitaminosis D is prevalent in pregnancy. We systematically reviewed the evidence of the impact of vitamin D on lung development, surfactant synthesis, RDS and BPD searching Pub...

  11. Prediction of fetal lung immaturity using gestational age, patient characteristics and fetal lung maturity tests: a probabilistic approach

    NARCIS (Netherlands)

    Wijnberger, L.D.E.; de Kleine, M.; Voorbij, H.A.M.; Arabin, B.; Bruinse, H.W.; Visser, G.H.A.; Bossuyt, P.M.M.; Mol, B.W.J.

    2010-01-01

    OBJECTIVES: The lecithin/sphingomyelin (L/S) ratio and the lamellar body count (LBC) can be used to predict respiratory distress syndrome (RDS). DESIGN: We performed a retrospective cohort study among consecutive women who underwent amniotic fluid sampling for the assessment of fetal lung maturity.

  12. LGL1 modulates proliferation, apoptosis, and migration of human fetal lung fibroblasts.

    Science.gov (United States)

    Zhang, Hui; Sweezey, Neil B; Kaplan, Feige

    2015-02-15

    Rapid growth and formation of new gas exchange units (alveogenesis) are hallmarks of the perinatal lung. Bronchopulmonary dysplasia (BPD), common in very premature infants, is characterized by premature arrest of alveogenesis. Mesenchymal cells (fibroblasts) regulate both lung branching and alveogenesis through mesenchymal-epithelial interactions. Temporal or spatial deficiency of late-gestation lung 1/cysteine-rich secretory protein LD2 (LGL1/CRISPLD2), expressed in and secreted by lung fibroblasts, can impair both lung branching and alveogenesis (LGL1 denotes late gestation lung 1 protein; LGL1 denotes the human gene; Lgl1 denotes the mouse/rat gene). Absence of Lgl1 is embryonic lethal. Lgl1 levels are dramatically reduced in oxygen toxicity rat models of BPD, and heterozygous Lgl1(+/-) mice exhibit features resembling human BPD. To explore the role of LGL1 in mesenchymal-epithelial interactions in developing lung, we developed a doxycycline (DOX)-inducible RNA-mediated LGL1 knockdown cellular model in human fetal lung fibroblasts (MRC5(LGL1KD)). We assessed the impact of LGL1 on cell proliferation, cell migration, apoptosis, and wound healing. DOX-induced MRC5(LGL1KD) suppressed cell growth and increased apoptosis of annexin V(+) staining cells and caspase 3/7 activity. LGL1-conditioned medium increased migration of fetal rat primary lung epithelial cells and human airway epithelial cells. Impaired healing by MRC5(LGL1KD) cells of a wound model was attenuated by addition of LGL1-conditioned medium. Suppression of LGL1 was associated with dysregulation of extracellular matrix genes (downregulated MMP1, ColXVα1, and ELASTIN) and proapoptosis genes (upregulated BAD, BAK, CASP2, and TNFRSF1B) and inhibition of 44/42MAPK phosphorylation. Our findings define a role for LGL1 in fibroblast expansion and migration, epithelial cell migration, and mesenchymal-epithelial signaling, key processes in fetal lung development.

  13. Autoradiographic localization of specific [3H]dexamethasone binding in fetal lung.

    Science.gov (United States)

    Beer, D G; Butley, M S; Cunha, G R; Malkinson, A M

    1984-10-01

    The cellular and subcellular localization of specific [3H]dexamethasone binding was examined in fetal mouse lung at various stages of development and in human fetal lung at 8 weeks of gestation using a rapid in vitro steroid incubation technique followed by thaw-mount autoradiography. Competition studies with unlabeled steroids demonstrate the specificity of [3H]dexamethasone labeling, and indicate that fetal lung mesenchyme is a primary glucocorticoid target during lung development. Quantitative binding studies, involving incubation of intact tissue with competing ligand and subsequent subcellular fractionation, show this to be specific, nuclear binding characteristic of glucocorticoid receptors. Autoradiographs of [3H]dexamethasone binding in lung tissue at early stages of development demonstrate that the mesenchyme directly adjacent to the more proximal portions of the bronchiolar network is heavily labeled. In contrast, the epithelium which will later differentiate into bronchi and bronchioles, is relatively unlabeled. Distal portions of the growing epithelium, destined to become alveolar ducts and alveoli, do show nuclear localization of [3H]dexamethasone. Because of the known importance of the mesenchyme in controlling lung development and the ability of glucocorticoids to stimulate lung development, these results suggest that many of the growth-promoting effects of glucocorticoids may be mediated through the mesenchyme. In addition, by utilizing a technique which allows the simultaneous examination of extracellular matrix components and [3H]dexamethasone binding, a relationship is observed between extensive mesenchymal [3H]dexamethasone binding and extensive extracellular matrix accumulation. Since glucocorticoids stimulate the synthesis of many extracellular matrix components, these results suggest a role for these hormones in affecting mesenchymal-epithelial interactions during lung morphogenesis.

  14. Fetal magnetic resonance imaging. Diagnostics in cases of congenital cystadenomatoid malformation; Fetale Magnetresonanztomographie. Diagnostik bei zystadenomatoider Malformation der Lunge (CCAM)

    Energy Technology Data Exchange (ETDEWEB)

    Buesing, K.A.; Kilian, A.K.; Neff, K.W. [Fakultaet fuer Klinische Medizin der Universitaet Heidelberg, Institut fuer Klinische Radiologie, Universitaetsklinikum Mannheim, Mannheim (Germany); Schaible, T. [Fakultaet fuer Klinische Medizin der Universitaet Heidelberg, Kinderklinik, Universitaetsklinikum Mannheim, Mannheim (Germany)

    2006-02-15

    Despite advancing therapeutic strategies, congenital cystadenomatoid malformation of the fetal lung is still a potentially life-threatening anomaly. Antenatally, the development of hydrops as well as the natural history of the malformation is of particular therapeutic and prognostic importance. Postnatally, respiratory distress due to pulmonary hypoplasia counts as a crucial limiting factor. Owing to its feasibility and practicability, as well as a high sensitivity, antenatal ultrasound is still the screening method of choice for the detection of fetal thoracic malformations. However, particularly in cases of indistinguishable sonographic findings, fetal MRI is the modality of choice for proving the diagnosis and preliminary appraisal of intensive care therapy and extracorporal membrane oxygenation postnatally. Furthermore, fetal MRI often facilitates assessment and planning of intrauterine surgical procedures. These two features frequently require a close transfer to an expert neonatal centre. (orig.) [German] Trotz verbesserter Therapien stellt die kongenitale zystadenomatoide Malformation der Lunge fuer den Feten weiterhin eine potenziell lebensbedrohliche Missbildung dar. Praenatal sind insbesondere ein Hydrops fetalis sowie der Spontanverlauf von prognostischer und therapeutischer Relevanz. Postnatal kommt der Lungenhypoplasie eine entscheidende Bedeutung zu. Aufgrund der hohen Verfuegbarkeit und Sensitivitaet bleibt die Primaerdiagnostik weiterhin dem Ultraschall vorbehalten. Die fetale MRT hingegen hat sich insbesondere bei unklarer sonographischer Befundlage als Methode der Wahl etabliert. Neben der Diagnosesicherung erleichtert sie durch eine uebersichtliche Darstellung der Befundausdehnung haeufig die Abschaetzung einer postnatalen Intensivtherapie. Mit zunehmender Erfahrung beim Einsatz fetalchirurgischer Verfahren kommt ihr ferner eine wachsende Bedeutung in der Indikationsstellung und Planung praenataler Therapien zu. Beides erfordert u. U. die

  15. Fetal cystic lung lesions: evaluation with magnetic resonance imaging.

    Science.gov (United States)

    Liu, Yu-Peng; Chen, Chih-Ping; Shih, Shin-Lin; Chen, Yi-Fang; Yang, Fei-Shih; Chen, Su-Chiu

    2010-06-01

    To investigate the contribution of magnetic resonance imaging (MRI) to the diagnosis of fetal cystic lung lesions found on routine prenatal ultrasound (US). Experienced radiologists retrospectively reviewed 34 fetal MRI studies performed in 20 fetuses (from 20 to 35 gestational weeks; including 14 repeat studies 10 weeks after the initial MRI), focusing on shape, signal characteristics, feeding artery, volume change, and location of the cystic lesions. Diagnoses were confirmed after birth by postnatal multidetector computed tomography (MDCT) and/or surgery. Bronchopulmonary sequestration (BPS) in the second trimester appeared as a well-defined, homogeneous, hyperintense mass (pure BPS) in eight cases or as a lobulated, inhomogeneous hyperintense mass (BPS mixed with congenital cystic adenomatoid malformation (CCAM)) in three cases. The feeding artery was visible in all 11 cases in the initial MRI, and regression of the mass was seen in 7 cases. As the mass regressed in the third trimester, the signal intensity decreased, becoming inhomogeneous, and the margins became lobulated. The mean initial ratio of the volume of the BPS lesion to the ipsilateral lung in lesions with partial regression was 82%; the mean initial ratio in lesions with nearly complete regression was 61%. CCAM (6) cases also appeared as a hyperintense lobulated mass, and as the lesions regressed, they decreased in size and signal intensity. As with BPS, the larger the lesion on initial MRI, the less likely it was to regress completely. Congenital lobar fluid overload in three cases appeared as a hyperintense, homogeneous lobe with stretched hilar vessels. Prenatal MRI is useful as a diagnostic tool complementary to US for evaluating fetal cystic lung lesions. Smaller lung lesions (<60%) may regress completely.

  16. Role of the adrenal glands in the maturation of lung liquid secretory mechanisms in fetal sheep.

    Science.gov (United States)

    Wallace, M J; Hooper, S B; Harding, R

    1996-01-01

    Our aim was to determine the role of the fetal adrenal glands in the gestational age-related increase in the ability of epinephrine to induce the reabsorption of lung liquid. Fetal lung liquid volumes and secretion rates were measured in five chronically catheterized control and six bilaterally adrenalectomized (ADX) fetal sheep at approximately 5-day intervals from 120 to 144 days of gestation (term approximately 146 days). The ability of epinephrine to induce the reabsorption of fetal lung liquid was then determined on day 144. Fetal adrenalectomy prevented the preparturient increase in fetal plasma cortisol and 3,5,3'-triiodothyronine (T3) concentration and significantly reduced the gestational age-related increase in fetal lung liquid volumes and secretion rates. Close to term (144 days), epinephrine infusions caused a significantly greater rate of lung liquid reabsorption in control (32.2 +/- 4.8 ml/h) compared with ADX (3.7 +/- 0.7 ml/h) fetuses. We conclude that the presence of the fetal adrenal glands is necessary for the age-related increase in 1) the lung liquid secretion rate and 2) the ability of the fetal lung to reabsorb liquid late in gestation. It is likely that cortisol is the active adrenal hormone involved, supporting the theory that cortisol plays a crucial role in the clearance of lung liquid at birth.

  17. Fetal lung dysplasia: clinical outcome based on a new classification system.

    Science.gov (United States)

    Achiron, R; Zalel, Y; Lipitz, S; Hegesh, J; Mazkereth, R; Kuint, J; Jacobson, J; Yagel, S

    2004-08-01

    To evaluate the clinical application of a new classification system of fetal lung anomalies. Forty fetal diagnoses of lung lesions were analyzed according to our proposed classification system in which each lung component is considered using two-dimensional ultrasound and color and power Doppler technology. Medical files, natural history and neonatal follow-up were recorded. Type I dysplasia: Four cases of agenesis of the lung were diagnosed, three with right lung agenesis and one with left lung agenesis. Three of the four patients elected to undergo termination of pregnancy (TOP). The surviving fetus was diagnosed with scimitar syndrome and postnatal embolization of the aberrant vessel was performed. Type II dysplasia: One case of normal lung with abnormal systemic feeding artery was diagnosed with normal neonatal outcome. Type III dysplasia: Abnormal lung with abnormal vascularity was found in 14 cases, presenting in most cases as echogenic lung masses. Seven were supradiaphragmatic, six subdiaphragmatic and one case was of undetermined position. All 14 fetuses showed an aberrant systemic artery emerging from the aorta. Abnormal venous drainage could be identified in only five (36%) of the fetuses: three had prominent azygos vein, one showed drainage to the inferior vena cava and one had multiple intrapulmonary veins forming a huge arteriovenous (A-V) shunt. Two cases in this group underwent TOP, the case with A-V shunt following development of hydrops, and one on maternal request. The remaining 12 fetuses (86%) survived and were alive and well at the time of writing; only one of them needed immediate postnatal embolization of the bilateral aberrant feeding arteries. Type IV dysplasia: Abnormal lung with no vascular abnormality was diagnosed in 20 fetuses. In this group there was one case of intrauterine fetal death, two patients underwent TOP, one complicated with hydrops and one on maternal request. The survival rate in this group was 85%. Only two cases needed

  18. Why do we need more data on MR volumetric measurements of the fetal lung?

    Energy Technology Data Exchange (ETDEWEB)

    Rubesova, Erika [Stanford University, Pediatric Radiology, Lucile Packard Children' s Hospital at Stanford, Stanford, CA (United States)

    2016-02-15

    Fetal lung hypoplasia is associated with a series of congenital anomalies, particularly the congenital diaphragmatic hernia. Evaluation of the severity of the lung hypoplasia is important for parental counseling, assessment of prognosis and planning of postnatal management. Although a large number of studies have been performed to measure fetal lung volumes in order to predict outcome, there are little data on fetuses younger than 24 weeks of gestation, the age when parental counseling is crucial if termination is considered. Few studies have evaluated prognosis of lung hypoplasia in fetuses with congenital chest anomalies other than congenital diaphragmatic hernia. We review the studies on measurements of the fetal lung volumes by MRI. (orig.)

  19. The innate immune response in fetal lung mesenchymal cells targets VEGFR2 expression and activity.

    Science.gov (United States)

    Medal, Rachel M; Im, Amanda M; Yamamoto, Yasutoshi; Lakhdari, Omar; Blackwell, Timothy S; Hoffman, Hal M; Sahoo, Debashis; Prince, Lawrence S

    2017-06-01

    In preterm infants, soluble inflammatory mediators target lung mesenchymal cells, disrupting airway and alveolar morphogenesis. However, how mesenchymal cells respond directly to microbial stimuli remains poorly characterized. Our objective was to measure the genome-wide innate immune response in fetal lung mesenchymal cells exposed to the bacterial endotoxin lipopolysaccharide (LPS). With the use of Affymetrix MoGene 1.0st arrays, we showed that LPS induced expression of unique innate immune transcripts heavily weighted toward CC and CXC family chemokines. The transcriptional response was different between cells from E11, E15, and E18 mouse lungs. In all cells tested, LPS inhibited expression of a small core group of genes including the VEGF receptor Vegfr2 Although best characterized in vascular endothelial populations, we demonstrated here that fetal mouse lung mesenchymal cells express Vegfr2 and respond to VEGF-A stimulation. In mesenchymal cells, VEGF-A increased cell migration, activated the ERK/AKT pathway, and promoted FOXO3A nuclear exclusion. With the use of an experimental coculture model of epithelial-mesenchymal interactions, we also showed that VEGFR2 inhibition prevented formation of three-dimensional structures. Both LPS and tyrosine kinase inhibition reduced three-dimensional structure formation. Our data suggest a novel mechanism for inflammation-mediated defects in lung development involving reduced VEGF signaling in lung mesenchyme. Copyright © 2017 the American Physiological Society.

  20. MRI investigation of normal fetal lung maturation using signal intensities on different imaging sequences.

    Science.gov (United States)

    Balassy, Csilla; Kasprian, Gregor; Brugger, Peter C; Weber, Michael; Csapo, Bence; Mittermayer, Christoph; Hörmann, Marcus; Prayer, Daniela

    2007-03-01

    To purpose of this paper is to study the relation between normal lung maturation signal and changes in intensity ratios (SIR) and to determine which magnetic resonance imaging sequence provides the strongest correlation of normal lung SIs with gestational age. 126 normal singleton pregnancies (20-37 weeks) were examined with a 1.5 Tesla unit. Mean SIs for lungs, liver, and gastric fluid were assessed on six different sequences, and SIRs of lung/liver (LLSIR) and lung/gastric fluid (LGSIR) were correlated with gestational age for each sequence. To evaluate the feasibility of SIRs in the prediction of the state of the lung maturity, accuracy of the predicted SIRs (D*) was measured by calculating relative residuals (D*-D)/D for each sequence. LLSIRs showed significant changes in every sequence (p<0.05), while LGSIRs only on two sequences. Significant differences were shown for the mean of absolute residuals for both LLSIRs (p<0.001) and for LGSIRs (p=0.003). Relative residuals of LLSIRs were significantly smaller on T1-weighted sequence, whereas they were significantly higher for LGSIRs on FLAIR sequence. Fetal liver seems to be adequate reference for the investigation of lung maturation. T1-weighted sequence was the most accurate for the measurement of the lung SIs; thus, we propose to determine LLSIR on T1-weighted sequence when evaluating lung development.

  1. MRI investigation of normal fetal lung maturation using signal intensities on different imaging sequences

    Energy Technology Data Exchange (ETDEWEB)

    Balassy, Csilla; Kasprian, Gregor; Weber, Michael; Hoermann, Marcus; Prayer, Daniela [Medical University of Vienna, Department of Radiology, Vienna (Austria); Brugger, Peter C. [Medical University of Vienna, Center of Anatomy and Cell Biology, Vienna (Austria); Csapo, Bence [Medical University of Vienna, Department of Obstetrics and Gyneocology, Vienna (Austria); Mittermayer, Christoph [Medical University of Vienna, Department of Pediatrics, Vienna (Austria)

    2007-03-15

    To purpose of this paper is to study the relation between normal lung maturation signal and changes in intensity ratios (SIR) and to determine which magnetic resonance imaging sequence provides the strongest correlation of normal lung SIs with gestational age. 126 normal singleton pregnancies (20-37 weeks) were examined with a 1.5 Tesla unit. Mean SIs for lungs, liver, and gastric fluid were assessed on six different sequences, and SIRs of lung/liver (LLSIR) and lung/gastric fluid (LGSIR) were correlated with gestational age for each sequence. To evaluate the feasibility of SIRs in the prediction of the state of the lung maturity, accuracy of the predicted SIRs (D*) was measured by calculating relative residuals (D*-D)/D for each sequence. LLSIRs showed significant changes in every sequence (p<0.05), while LGSIRs only on two sequences. Significant differences were shown for the mean of absolute residuals for both LLSIRs (p<0.001) and for LGSIRs (p=0.003). Relative residuals of LLSIRs were significantly smaller on T1-weighted sequence, whereas they were significantly higher for LGSIRs on FLAIR sequence. Fetal liver seems to be adequate reference for the investigation of lung maturation. T1-weighted sequence was the most accurate for the measurement of the lung SIs; thus, we propose to determine LLSIR on T1-weighted sequence when evaluating lung development. (orig.)

  2. Fetal lung lesions diagnosis: the crucial role of ultrasonography

    Science.gov (United States)

    Pedata, Rosa; Palermo, Mariarosaria; Maiello, Monica; Esposito, Nunzia; Ermito, Santina; Dinatale, Angela; Carrara, Sabina; Cavaliere, Alessandro

    2009-01-01

    Fetal lung lesions may cause significant effects of mass and may evolve into a non-immune hydrops and lead to the death of the fetus or the child. Treatment options for these severely affected infants are constantly evolving. The widespread use of ultrasound in prenatal diagnosis, in tertiary center like ours, allows us to identify the fetus, including lung lesions more ‘small. Prenatal diagnosis and possible therapeutic intervention in the immediate prenatal or postnatal period has significantly changed the quality of life and the survival of fetuses and infants, especially those who were completely asymptomatic at birth. Object of our interest is the pulmonary sequestration and congenital pulmonary malformation is the second in order of frequency, with an incidence between 0.15% and 6.4% of cases. PMID:22439045

  3. Alterations in maternal corticosteroid levels influence fetal urine and lung liquid production.

    Science.gov (United States)

    Jensen, Ellen; Wood, Charles E; Keller-Wood, Maureen

    2003-12-01

    This study was designed to test the hypotheses that disruption of maternal adrenal secretion in late pregnancy requires fetal adaptations in order to maintain fetal blood volume and fetal viability. Pregnant ewes were adrenalectomized at approximately 112 days, and cortisol and aldosterone were replaced to either normal pregnant levels (with 1 mg/kg per day of cortisol and 3 microg/kg per day of aldosterone) or normal nonpregnant levels of aldosterone or cortisol (0.5 mg/kg per day of cortisol or 1.5 microg/kg per day of aldosterone). Fetal blood volume, blood pressure, lung liquid production, urine production, free water clearance, and glomerular filtration rate were measured at 130 days. In a separate group, fetal organ blood flow was measured. Fetal blood volume was not significantly decreased by disruption of maternal corticosteroid secretion. However fetal urine production and free water clearance were reduced in fetuses of low cortisol or low aldosterone ewes. Fetal lung liquid secretion was also significantly reduced in the low aldosterone group. The glomerular filtration rate was reduced in fetuses of all adrenalectomized ewes, regardless of replacement dose. Fetal blood pressure was significantly reduced in the fetuses of low aldosterone ewes; blood flow to several fetal organs was increased in this group, indicating that decreased vascular resistance may contribute to the relative hypotension. Alterations in maternal adrenal corticosteroid levels resulted in fetal adaptation to maintain fetal blood volume despite relative maternal hypovolemia. These adaptations occurred at the expense of fetal urine and lung liquid production.

  4. DANCE in developing and injured lung.

    Science.gov (United States)

    Jean, Jyh-Chang; Eruchalu, Ifeanyi; Cao, Yu Xia; Joyce-Brady, Martin

    2002-01-01

    We identified rat developing arteries and neural crest derivatives with multiple epidermal growth factor-like domains (DANCE) as a developmentally regulated gene using suppression-subtractive hybridization. Northern analysis confirmed a fivefold induction of this mRNA transcript between fetal day 18 and 20 that persisted through postnatal day 17. The level was declining at postnatal day 21 and was similar in adult lung to that at fetal day 18. In adults DANCE mRNA abundance was highest in lung, kidney, and spleen, lower in heart, skeletal muscle, and brain, but absent from liver and thymus. It was abundant in pulmonary artery endothelium and a lung epithelial type 2 cell line, barely detectable in vascular smooth muscle, and absent in fibroblasts. In situ hybridization revealed a regulated pattern of expression in endothelial cells of fetal, postnatal, and adult lung. Because DANCE mRNA was inducible in systemic arteries during recovery from injury, we searched for induction in lung injured by hyperoxia. Mouse DANCE mRNA abundance was unchanged during an acute 3-day exposure period, induced threefold 5 days into the recovery phase, and returned to baseline at days 8, 11, and 14. In situ hybridization at day 5 suggested a diffuse pattern of induction. DANCE may play a role in lung endothelial cell biology during development repair after injury.

  5. Insulin dose during glucocorticoid treatment for fetal lung maturation in diabetic pregnancy: test of an algorithm [correction of analgoritm

    DEFF Research Database (Denmark)

    Mathiesen, Elisabeth R; Christensen, Ann-Birgitte L; Hellmuth, Ellinor

    2002-01-01

    Poor glycemic control is often a serious clinical problem during glucocorticoid treatment for fetal lung maturation in pregnant women with diabetes. An algorithm for improved subcutaneous insulin treatment during glucocorticoid treatment in insulin-dependent diabetic women was developed and tested....

  6. Effect of Bile Acid on Fetal Lung in Rat Model of Intrahepatic Cholestasis of Pregnancy

    Directory of Open Access Journals (Sweden)

    Ling Yu

    2014-01-01

    Full Text Available Objective. To determine the correlation between maternal bile acid (BA level and fetal pulmonary surfactant in rats and study the effects of BA on fetal lung in rat model of intrahepatic cholestasis of pregnancy. Methods. Forty pregnant rats were treated with (A 5.5 mg/kg BA, (B 1.4 mg/kg BA, and (C 1 ml physiological saline. Levels of total bile acid (TBA, ALT, AST, TBIL, DBIL, and SP-A were determined and the lungs of fetal rats were analyzed for pathological changes. Results. Groups A and B intervened with BA showed significant higher level of TBA in both maternal and fetal serum, more mortality rate of fetal rats, more concentration of SP-A in fetal serum, and wider alveolus mesenchyme of fetal rats than the control Group C. Higher level of BA associated with increased fetal risk and lower numerical density of mitochondria in type II alveolar epithelial cells. The levels of TBA in maternal serum were found to have significant positive correlation with those in fetal serum and SP-A level but negatively with the area of alveolus and the numerical density of lamellar body. Conclusions. The TBA level in maternal serum showed significant association with lung pathological changes in fetal rats.

  7. The prognostic factors in the prenatal diagnosis of the echogenic fetal lung.

    Science.gov (United States)

    Barret, J; Chitayat, D; Sermer, M; Amankwah, K; Morrow, R; Toi, A; Ryan, G

    1995-09-01

    The prenatal diagnosis of an echogenic fetal lung (EFL) is now often made in the early second trimester using high-resolution ultrasound. This ultrasound appearance is usually caused by a congenital cystic adenomatoid lung malformation (CCAM), an intrapulmonary lung sequestration or obstruction of a major airway. In order to provide prognostic guidelines to parents who may be considering termination of a fetus with these findings, we have analysed a series of 11 cases diagnosed in our centre over the past 2 years in conjunction with 60 cases from major published series. The data suggest that in the absence of non-immune hydrops fetalis (NIHF) or other anomalies, the outcome for the fetuses is excellent, with over 90 per cent survival. Neither early diagnosis (24 weeks) nor the presence of mediastinal shift is a poor prognostic indicator. In addition, it appears that if NIHF is absent at diagnosis, the chance that it will develop as the pregnancy continues is small (6 per cent). Furthermore, there is a significant (up to 30 per cent) chance that this ultrasound finding will resolve in utero. The development of in utero fetal surgical techniques may be the only hope for those hydropic fetuses who appear to have a dismal prognosis.

  8. Overexpression of transforming growth factor-beta1 in fetal monkey lung results in prenatal pulmonary fibrosis.

    Science.gov (United States)

    Tarantal, A F; Chen, H; Shi, T T; Lu, C-H; Fang, A B; Buckley, S; Kolb, M; Gauldie, J; Warburton, D; Shi, W

    2010-10-01

    Altered transforming growth factor (TGF)-β expression levels have been linked to a variety of human respiratory diseases, including bronchopulmonary dysplasia and pulmonary fibrosis. However, a causative role for aberrant TGF-β in neonatal lung diseases has not been defined in primates. Exogenous and transient TGF-β1 overexpression in fetal monkey lung was achieved by transabdominal ultrasound-guided fetal intrapulmonary injection of adenoviral vector expressing TGF-β1 at the second or third trimester of pregnancy. The lungs were then harvested near term, and fixed for histology and immunohistochemistry. Lung hypoplasia was observed where TGF-β1 was overexpressed during the second trimester. The most clearly marked phenotype consisted of severe pulmonary and pleural fibrosis, which was independent of the gestational time point when TGF-β1 was overexpressed. Increased cell proliferation, particularly in α-smooth muscle actin-positive myofibroblasts, was detected within the fibrotic foci. But epithelium to mesenchyme transdifferentiation was not detected. Massive collagen fibres were deposited on the inner and outer sides of the pleural membrane, with an intact elastin layer in the middle. This induced fibrotic pathology persisted even after adenoviral-mediated TGF-β1 overexpression was no longer evident. Therefore, overexpression of TGF-β1 within developing fetal monkey lung results in severe and progressive fibrosis in lung parenchyma and pleural membrane, in addition to pulmonary hypoplasia.

  9. Maternal smoking and fetal lung signals--an in utero MRI investigation.

    Science.gov (United States)

    Schmid, Maximilian; Marschalek, Julian; Springer, Stephanie; Klein, Katharina; Kasprian, Gregor; Prayer, Daniela

    2012-03-01

    To investigate whether fetal lung signals and fetal lung signal progression over gestation observed on magnetic resonance imaging are different in mothers who reported smoking during pregnancy compared with nonsmoking controls. Cross-sectional retrospective study of 100 consecutive singleton pregnancies that underwent magnetic resonance imaging. Fetal lung-liver signal intensity ratios of 18 fetuses of mothers who reported smoking during pregnancy were compared with 82 fetuses of nonsmoking controls. Average gestational age at magnetic resonance imaging was 26.4 ± 5.2 weeks (Range 18.4-38.2 weeks). Cases reported smoking between 2 and 15 cigarettes per day. The mean number of cigarettes per day for cases was 9.2 ± 3.4. Mean fetal lung-liver signal intensity ratios did not differ significantly between the two groups (p = 0.8). They showed a linear increase with gestational age (r(2) = 0.3). Multiple regression analysis of lung-liver signal intensity ratios using gestational age and smoking status as predictors revealed a significant influence of gestational age (p < 0.0001) but not maternal smoking status (p = 0.8) on fetal lung-liver signal intensity ratios. Fetuses of mothers who reported smoking during pregnancy show similar lung signals and lung signal progression over gestation on magnetic resonance imaging as nonsmoking controls. © 2012 John Wiley & Sons, Ltd.

  10. Expression of nestin in human fetal lung%巢蛋白在人胚胎肺中的表达

    Institute of Scientific and Technical Information of China (English)

    董丽萍; 邹鹰; 黄河; 张喆; 魏楚蓉; 伍赶球

    2011-01-01

    目的:研究不同时期人胚胎肺中巢蛋白的表达变化,探讨巢蛋白在肺发育过程中的作用.方法:取3~8月人胚胎肺组织,常规石蜡切片,采用免疫组织化学法检测巢蛋白在胚胎肺中的表达及分布.结果:各胎龄段(3~8月)肺均有巢蛋白的表达,巢蛋白阳性细胞主要分布于肺内支气管旁和血管中,而在支气管上皮中未发现阳性细胞.结论:正常人胚胎肺中有巢蛋白的表达,随着胎龄的增加,巢蛋白表达量下降.%Objective To study the changes of expression of nestin in fetal lung and to explore the function of nestin during lung development in human. Methods Fetal lung tissues from 3-8 months' embryos were dissected and fixed for paraffin section. Immunohistochemical staining was proceeded to examine the expression level and distribution of nestin in fetal lung. Results Nestin was highly expressed strongly throughout lung in human fetal of 3 - 8 months' embryos. Nestin-positive cells distributed in pulmonary, entobronchus and blood vessels, but it was not found in bronchial epithelium. Conclusion Nestin widely expresses in normal human fetal lung. The level of expression decreases with the increase of gestational age.

  11. Development of cholinephosphotransferase in guinea pig lung mitochondria and microsomes.

    Science.gov (United States)

    Stith, I E; Das, S K

    1982-02-02

    Development of mitochondrial and microsomal choline phosphotransferase in the fetal guinea pig lung was investigated. The activity in fetal mitochondria was more than twice of that in fetal microsomes. However, in adult lung, the enzyme was distributed mostly in microsomes. In fetal lung, both the mitochondrial and microsomal enzyme activity was greatest at approx. 81% of the total gestation period (55 days). The specific activity in the microsomal fraction than declined until term, but increased again in the 24-h newborn from 1.0 to 2.3 nmol/min per mg protein. The activity in the mitochondrial fraction declined after 61 days (2.8 nmol/min per mg) to a minimal level at term (0.6 nmol/min per mg). Although the enzyme activity decreased from day 55 (1.2 nmol/min per mg), the amount of phosphatidylcholine gradually increased between day 55 and term.

  12. Spontaneous peristaltic airway contractions propel lung liquid through the bronchial tree of intact and fetal lung explants.

    Science.gov (United States)

    Schittny, J C; Miserocchi, G; Sparrow, M P

    2000-07-01

    Spontaneous contractions of the fetal airways are a well recognized but poorly characterized phenomenon. In the present study spontaneous narrowing of the airways was analyzed in freshly isolated lungs from early to late gestation in fetal pigs and rabbits and in cultured fetal mouse lungs. Propagating waves of contraction traveling proximal to distal were observed in fresh lungs throughout gestation which displaced the lung liquid along the lumen. In the pseudoglandular and canalicular stages (fetal pigs) the frequency ranged from 2.3 to 3.3 contractions/min with a 39 to 46% maximum reduction of lumen diameter. In the saccular stage (rabbit) the frequency was 10 to 12/min with a narrowing of approximately 30%. In the organ cultures the waves of narrowing started at the trachea in whole lungs, or at the main bronchus in lobes (5.2 +/- 1.5 contractions/min, 22 +/- 8% reduction of lumen diameter), and as they proceeded distally along the epithelial tubes the luminal liquid was shifted toward the terminal tubules, which expanded the endbuds. As the tubules relaxed the flow of liquid was reversed. Thus the behavior of airway smooth muscle in the fetal lung is phasic in type (like gastrointestinal muscle) in contrast to that in postnatal lung, where it is tonic. An intraluminal positive pressure of 2.33 +/- 0.77 cm H(2)O was recorded in rabbit fetal trachea. It is proposed that the active tone of the smooth muscle maintains the positive intraluminal pressure and acts as a stimulus to lung growth via the force exerted across the airway wall and adjacent parenchyma. The expansion of the compliant endbuds by the fluid shifts at the airway tip may promote their growth into the surrounding mesenchyme.

  13. Inflammation and lung maturation from stretch injury in preterm fetal sheep.

    Science.gov (United States)

    Hillman, Noah H; Polglase, Graeme R; Pillow, J Jane; Saito, Masatoshi; Kallapur, Suhas G; Jobe, Alan H

    2011-02-01

    Mechanical ventilation is a risk factor for the development of bronchopulmonary dysplasia in premature infants. Fifteen minutes of high tidal volume (V(T)) ventilation induces inflammatory cytokine expression in small airways and lung parenchyma within 3 h. Our objective was to describe the temporal progression of cytokine and maturation responses to lung injury in fetal sheep exposed to a defined 15-min stretch injury. After maternal anesthesia and hysterotomy, 129-day gestation fetal lambs (n = 7-8/group) had the head and chest exteriorized. Each fetus was intubated, and airway fluid was gently removed. While placental support was maintained, the fetus received ventilation with an escalating V(T) to 15 ml/kg without positive end-expiratory pressure (PEEP) for 15 min using heated, humidified 100% nitrogen. The fetus was then returned to the uterus for 1, 6, or 24 h. Control lambs received a PEEP of 2 cmH(2)O for 15 min. Tissue samples from the lung and systemic organs were evaluated. Stretch injury increased the early response gene Egr-1 and increased expression of pro- and anti-inflammatory cytokines within 1 h. The injury induced granulocyte/macrophage colony-stimulating factor mRNA and matured monocytes to alveolar macrophages by 24 h. The mRNA for the surfactant proteins A, B, and C increased in the lungs by 24 h. The airway epithelium demonstrated dynamic changes in heat shock protein 70 (HSP70) over time. Serum cortisol levels did not increase, and induction of systemic inflammation was minimal. We conclude that a brief period of high V(T) ventilation causes a proinflammatory cascade, a maturation of lung monocytic cells, and an induction of surfactant protein mRNA.

  14. Maternal smoking and fetal lung volume-an in utero MRI investigation.

    Science.gov (United States)

    Schmid, Maximilian; Kasprian, Gregor; Marschalek, Julian; Posch, Angela; Balassy, Csilla; Prayer, Daniela

    2011-05-01

    To investigate whether fetal lung volume and fetal lung volume growth over gestation are different in mothers who reported smoking during pregnancy compared to non-smoking controls. Cross-sectional retrospective study of the data of 200 consecutive singleton pregnancies that underwent magnetic resonance imaging (MRI). Fetal lung volumes of 32 fetuses of mothers who reported smoking during pregnancy were compared to 168 fetuses of non-smoking controls. Cases reported smoking between 2 and 30 cigarettes per day. The mean number of cigarettes per day for cases was 10.2 ± 6.1. After logarithmic transformation, lung volumes showed a linear increase with gestational age (r(2) = 0.7). Multiple regression analysis revealed a significant influence of gestational age (p < 0.0001) but not maternal smoking status (p = 1.0) on fetal lung volumes. Comparison of the relative difference between observed and predicted lung volumes for both groups by means of unpaired t-test revealed no significant influence of maternal smoking status on this variable (p = 0.9). Fetuses of mothers who reported smoking during pregnancy show similar lung volumes and lung volume growth in MRI compared to non-smoking controls. Our data suggest that a reduced lung volume is not responsible for the increase in respiratory symptoms associated with prenatal smoking. Copyright © 2011 John Wiley & Sons, Ltd.

  15. Evaluation of Fetal Lung Ultrasound Images by Digital Texture Analysis Methods

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    Ümmu Yildiz

    2016-01-01

    Full Text Available Aim: Evaluation of fetal lung maturity in preterm pregnancies without requirement for an invasive procedure such as amniocentesis is of importance. The aim of the present study was to extract numerical features from fetal pulmonary ultrasound images, using computerized texture analysis methods. Material and Method: Twenty fetal ultrasound images from 18 pregnancies that were followed up in our department for threatened preterm delivery between 24-37 weeks of gestational age were included before corticosteroid administration. Transverse sections including well-defined visualization of bilateral fetal lungs without artifacts were evaluated. Regions of interests (ROIs with a 64x64 pixel area and homogenous pulmonary tissue were selected. Images were analyzed with invariant moments (IM, grey level co-occurrence matrix (GLCM, and wavelet analysis (WA using MATLAB R2014a computer software. Results: The mean gestational age was 30.9 ± 3.2 weeks. A total of 159 features were extracted from the ROIs of each image. Therefore, fetal ultrasound images were coded into numerical values, using advanced texture analysis techniques. Discussion: Assessment of ultrasound images from fetal lungs at different gestational ages was feasible with the introduced digital tissue analysis algorithm. Non-invasive evaluation of fetal lung maturity will subsequently be investigated in line with the defined procedure.

  16. Prenatal diagnosis of fetal respiratory function: evaluation of fetal lung maturity using lung-to-liver signal intensity ratio at magnetic resonance imaging.

    Science.gov (United States)

    Oka, Yasuko; Rahman, Mosfequr; Sasakura, Chihaya; Waseda, Tomoo; Watanabe, Yukio; Fujii, Ryota; Makinoda, Satoru

    2014-12-01

    The purpose of this retrospective study is to determine the fetal lung-to-liver signal intensity ratio (LLSIR) on T2-weighted images for the prediction of neonatal respiratory outcome. One hundred ten fetuses who underwent magnetic resonance imaging (MRI) examination for various indications after 22 weeks of gestation participated in this study. LLSIR was measured as the ratio of signal intensities of the fetal lung and liver on T2-weighted images at MRI. We examined the changes of the ratio with advancing gestation and the relations between LLSIR and the presence of the severe respiratory disorder (SRD) after birth. The best cut-off value of the LLSIR to predict respiratory outcome after birth was calculated using receiver operating characteristic (ROC) curve analysis. Lung-to-liver signal intensity ratio correlated significantly with advancing gestational age (R = 0.35, p fetal LLSIR on T2-weighted images is an accurate marker to diagnose the fetal lung maturity. © 2014 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd.

  17. Prenatal assessment of normal fetal pulmonary grey-scale and lung volume by three-dimensional ultrasonography

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Objective To quantitatively analyze the fetal lung echo and right lung volume in the third trimester by real-time three-dimensional ultrasound(3-D US)and evaluate the feasibility of fetal lung maturity.Methods A total of 732 women with normal singleton pregnancies between 28 and 42 weeks of gestation underwent ultrasound examination.The 3-D US equipment with a 3.5-5 MHz transabdominal transducer was used for the fetal biometric measurement.The echogenicity ratio between fetal lung and liver was compared.The...

  18. Hypoxia Inducible Factor: a breath of fresh air in lung development

    NARCIS (Netherlands)

    F.A. Groenman (Freek)

    2007-01-01

    textabstractChapter 1 is a general introduction to normal and abnormal lung development. It outlines the current state of knowledge of the molecular basis of normal fetal lung development and then discusses the importance of these molecules in aberrant human lung development. It highlights the

  19. Expression of genes related to the hypothalamic-pituitary-adrenal axis in murine fetal lungs in late gestation

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    Côté Mélissa

    2010-11-01

    Full Text Available Abstract Background Lung maturation is modulated by several factors, including glucocorticoids. Expression of hypothalamic-pituitary-adrenal (HPA axis-related components, with proposed or described local regulatory systems analogous to the HPA axis, was reported in peripheral tissues. Here, HPA axis-related genes were studied in the mouse developing lung during a period overlapping the surge of surfactant production. Methods Expression of genes encoding for corticotropin-releasing hormone (CRH, CRH receptors (CRHR 1 and 2beta, CRH-binding protein, proopiomelanocortin (POMC, melanocortin receptor 2 (MC2R, and glucocorticoid receptor was quantified by real-time PCR and localized by in situ hydridization in fetal lungs at gestational days (GD 15.5, 16.5, and 17.5, and was also quantified in primary mesenchymal- and epithelial cell-enriched cultures. In addition, the capability of CRH and adrenocorticotropic hormone (ACTH to stimulate pulmonary expression of enzymes involved in the adrenal pathway of glucocorticoid synthesis was addressed, as well as the glucocorticoid production by fetal lung explants. Results We report that all the studied genes are expressed in fetal lungs according to different patterns. On GD 15.5, Mc2r showed peaks in expression in samples that have previously presented high mRNA levels for glucocorticoid synthesizing enzymes, including 11beta-hydroxylase (Cyp11b1. Crhr1 mRNA co-localized with Pomc mRNA in cells surrounding the proximal epithelium on GD 15.5 and 16.5. A transition in expression sites toward distal epithelial cells was observed between GD 15.5 and 17.5 for all the studied genes. CRH or ACTH stimulation of genes involved in the adrenal pathway of glucocorticoid synthesis was not observed in lung explants on GD 15.5, whereas CRH significantly increased expression of 21-hydroxylase (Cyp21a1 on GD 17.5. A deoxycorticosterone production by fetal lung explants was observed. Conclusions Temporal and spatial

  20. MRI of normal fetal brain development.

    Science.gov (United States)

    Prayer, Daniela; Kasprian, Gregor; Krampl, Elisabeth; Ulm, Barbara; Witzani, Linde; Prayer, Lucas; Brugger, Peter C

    2006-02-01

    Normal fetal brain maturation can be studied by in vivo magnetic resonance imaging (MRI) from the 18th gestational week (GW) to term, and relies primarily on T2-weighted and diffusion-weighted (DW) sequences. These maturational changes must be interpreted with a knowledge of the histological background and the temporal course of the respective developmental steps. In addition, MR presentation of developing and transient structures must be considered. Signal changes associated with maturational processes can mainly be ascribed to the following changes in tissue composition and organization, which occur at the histological level: (1) a decrease in water content and increasing cell-density can be recognized as a shortening of T1- and T2-relaxation times, leading to increased T1-weighted and decreased T2-weighted intensity, respectively; (2) the arrangement of microanatomical structures to create a symmetrical or asymmetrical environment, leading to structural differences that may be demonstrated by DW-anisotropy; (3) changes in non-structural qualities, such as the onset of a membrane potential in premyelinating axons. The latter process also influences the appearance of a structure on DW sequences. Thus, we will review the in vivo MR appearance of different maturational states of the fetal brain and relate these maturational states to anatomical, histological, and in vitro MRI data. Then, the development of the cerebral cortex, white matter, temporal lobe, and cerebellum will be reviewed, and the MR appearance of transient structures of the fetal brain will be shown. Emphasis will be placed on the appearance of the different structures with the various sequences. In addition, the possible utility of dynamic fetal sequences in assessing spontaneous fetal movements is discussed.

  1. MRI of normal fetal brain development

    Energy Technology Data Exchange (ETDEWEB)

    Prayer, Daniela [Department of Radiodiagnostics, Medical University of Vienna, Vienna (Austria)]. E-mail: Daniela.prayer@meduniwien.ac.at; Kasprian, Gregor [Department of Radiodiagnostics, Medical University of Vienna, Vienna (Austria); Krampl, Elisabeth [Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna (Austria); Ulm, Barbara [Department of Prenatal Diagnosis, Medical University of Vienna, Vienna (Austria); Witzani, Linde [Department of Radiodiagnostics, Medical University of Vienna, Vienna (Austria); Prayer, Lucas [Diagnosezentrum Urania, Vienna (Austria); Brugger, Peter C. [Center of Anatomy and Cell Biology, Medical University of Vienna, Vienna (Austria)

    2006-02-15

    Normal fetal brain maturation can be studied by in vivo magnetic resonance imaging (MRI) from the 18th gestational week (GW) to term, and relies primarily on T2-weighted and diffusion-weighted (DW) sequences. These maturational changes must be interpreted with a knowledge of the histological background and the temporal course of the respective developmental steps. In addition, MR presentation of developing and transient structures must be considered. Signal changes associated with maturational processes can mainly be ascribed to the following changes in tissue composition and organization, which occur at the histological level: (1) a decrease in water content and increasing cell-density can be recognized as a shortening of T1- and T2-relaxation times, leading to increased T1-weighted and decreased T2-weighted intensity, respectively; (2) the arrangement of microanatomical structures to create a symmetrical or asymmetrical environment, leading to structural differences that may be demonstrated by DW-anisotropy; (3) changes in non-structural qualities, such as the onset of a membrane potential in premyelinating axons. The latter process also influences the appearance of a structure on DW sequences. Thus, we will review the in vivo MR appearance of different maturational states of the fetal brain and relate these maturational states to anatomical, histological, and in vitro MRI data. Then, the development of the cerebral cortex, white matter, temporal lobe, and cerebellum will be reviewed, and the MR appearance of transient structures of the fetal brain will be shown. Emphasis will be placed on the appearance of the different structures with the various sequences. In addition, the possible utility of dynamic fetal sequences in assessing spontaneous fetal movements is discussed.

  2. Selective exposure of the fetal lung and skin/amnion (but not gastro-intestinal tract) to LPS elicits acute systemic inflammation in fetal sheep.

    Science.gov (United States)

    Kemp, Matthew W; Kannan, Paranthaman Senthamarai; Saito, Masatoshi; Newnham, John P; Cox, Tom; Jobe, Alan H; Kramer, Boris W; Kallapur, Suhas G

    2013-01-01

    Inflammation of the uterine environment (commonly as a result of microbial colonisation of the fetal membranes, amniotic fluid and fetus) is strongly associated with preterm labour and birth. Both preterm birth and fetal inflammation are independently associated with elevated risks of subsequent short- and long-term respiratory, gastro-intestinal and neurological complications. Despite numerous clinical and experimental studies to investigate localised and systemic fetal inflammation following exposure to microbial agonists, there is minimal data to describe which fetal organ(s) drive systemic fetal inflammation. We used lipopolysaccharide (LPS) from E.coli in an instrumented ovine model of fetal inflammation and conducted a series of experiments to assess the systemic pro-inflammatory capacity of the three major fetal surfaces exposed to inflammatory mediators in pregnancy (the lung, gastro-intestinal tract and skin/amnion). Exposure of the fetal lung and fetal skin/amnion (but not gastro-intestinal tract) caused a significant acute systemic inflammatory response characterised by altered leucocytosis, neutrophilia, elevated plasma MCP-1 levels and inflammation of the fetal liver and spleen. These novel findings reveal differential fetal organ responses to pro-inflammatory stimulation and shed light on the pathogenesis of fetal systemic inflammation after exposure to chorioamnionitis.

  3. Fetal lung volume measurement by MRI with high-speed imaging systems

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    Osada, Hisao; Kaku, Kenshi [Chiba Univ. (Japan). Hospital

    2002-08-01

    Although ultrasonography is widely used for fetal morphologic observation, magnetic resonance imaging (MRI) has gained popularity as a new prenatal diagnostic method with recent introduction of high-speed imaging systems. Infants with lung hypoplasia affecting respiratory function require intensive management starting immediately after birth. Therefore, accurate prenatal differential diagnosis and severity evaluation are extremely important for these fetuses. The aim of this study is to measure fetal lung volume using a computer-based, three-dimensional MRI imaging system and to evaluate the possibility of clinical applications of this procedure. A total of 96 fetuses were evaluated, all were morphologically abnormal, and MRI was done for advanced assessment from 24 to 39 weeks gestation. Three-directional views of fetal chest were imaged by Signa Horizon, 1.5 Tesla, version 5.6 (General Electronics) with the following conditions; coil: TORSO coil, sequence: SSFSE (single shot fast spin echo), slice thickness: 5 mm, and imaging speed: 2 seconds/slice. To calculate the lung volume and create three-dimensional image, the lung area in each slice was traced out, then multiplied using computer image processing. Simultaneously, the volumes of all slices were summed to give the volume of each lung. Linear regression analysis and analysis of covariance (ANCOVA) were used for statistical analyses. In all cases, clear images were obtained, and were adequate for three-dimensional evaluation of the fetal lung. Thirty-five fetuses had poor outcomes, such as intrauterine fetal death, neonatal death, and intensive respiratory care. Regression lines of lung volume versus gestational week were calculated for these fetuses with poor outcome and 61 other fetuses with good outcome. ANCOVA, with gestational week as a covariant, revealed a significant intergroup difference in the lung volume (p<0.001). Similarly, regression lines of lung volume versus fetal body weight estimated by

  4. Intra-amniotic LPS modulation of TLR signaling in lung and blood monocytes of fetal sheep.

    Science.gov (United States)

    Kramer, Boris W; Kallapur, Suhas G; Moss, Timothy J; Nitsos, Ilias; Newnham, John P; Jobe, Alan H

    2009-04-01

    Epidemiological studies suggest that intra-uterine exposure to inflammation may prime postnatal immune responses. In fetal sheep, intra-amniotic injection of lipopolysaccharide (LPS) induced chorioamnionitis, lung inflammation and maturation, matured lung monocytes to macrophages and initiated systemic tolerance of fetal monocytes to subsequent challenge with LPS. We hypothesized that LPS-mediated chorioamnionitis altered the response of lung and blood monocytes to Toll-like receptor (TLR) ligands such as PamCysK4 (TLR2), flagellin (TLR5), and human CpG-DNA (TLR9). Time-mated ewes were given intra-amniotic injections of LPS or saline. Blood and lung monocytes were assessed after 2 days, 7 days and 2 days and 7 days repetitive LPS injections before delivery at 124 days gestational age (term 150 days). Responsiveness of blood and lung monocytes to TLR-ligands in vitro was assessed by interleukin (IL)-6, tumor necrosis factor-alpha (TNF-alpha) and hydrogen peroxide. Monocytes from preterm controls had minimal responses. Lipopolysaccharide-mediated chorioamnionitis increased IL-6, TNF- alpha and hydrogen peroxide to all TLR agonists in blood and lung monocytes. Repetitive exposure to antenatal LPS reduced IL-6, TNF- alpha and hydrogen peroxide to TLR-ligands suggesting tolerance. Tolerance to TLR-ligands reduced IL-1 receptor associated kinase-4 expression. Thus, repeated fetal exposure to LPS induced tolerance to other TLR-ligands. These modulations of fetal innate immunity have implications for host defense and injury responses in preterm infants.

  5. B12 in fetal development.

    Science.gov (United States)

    Pepper, M Reese; Black, Maureen M

    2011-08-01

    Vitamin B12 (cobalamin) is necessary for development of the fetus and child. Pregnant women who are vegetarian or vegan, have Crohn's or celiac disease, or have undergone gastric bypass surgery are at increased risk of B12 deficiency. Low serum levels of B12 have been linked to negative impacts in cognitive, motor, and growth outcomes. Low cobalamin levels also may be related to depression in adults. Some studies indicate that B12 supplementation may improve outcomes in children, although more research is needed in this area. Overall, the mechanisms of B12 action in development remain unclear. Further studies in this area to elucidate the pathways of cobalamin influence on development, as well as to prevent B12 deficiency in pregnant women and children are indicated.

  6. Comparative analysis of amniotic fluid lamellar body count and foam stability test as indices of fetal lung maturity

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    Višnjevac Nemanja

    2010-01-01

    Full Text Available Introduction. Respiratory distress syndrome of the newborn caused by the fetal lung immaturity is a very serious clinical problem. Different tests of prenatal analysis of amniotic fluid, such as lamellar body count and Clements’ test, are available for predicting the fetal lung maturity. Material and methods. A prospective clinical study was conducted on amniotic fluid samples from 2005 to 2006. The amniotic fluid samples were obtained at the gestational age of 30 to 42 weeks and collected by vaginal amniotomy, amniotomy during Caesarean section and 72 hours before the delivery by amniocentesis. A haematology analyzer (Nikon-Kohden® was used to determine the lamellar body counts. Clements’ test involved adding an equal volume of 96% ethanol to the multiple amniotic fluid volume (1:2, 1:4, 1:16, 1:32, followed by shaking and noting the presence of ring of bubbles. After the delivery, we compared the lamellar body count results and Clements’ test and the outcome of pregnancies, primarily the development of respiratory distress syndrome. The most specific lamellar body cutoffs for maturity and immaturity were determined according to receiver operating characteristic curves. Results and Discussion. Out of 232 amniotic fluid samples which were tested, 112 samples were collected after vaginal amniotomy, 88 during the Caesarean delivery and 32 samples by amniocentesis. The overall incidence of respiratory distress syndrome was 14.6%. Receiver operating characteristic curves were used to identify cutoff points for the test. We found that both tests are good screening tests for predicting the fetal lung maturity with the area under the curve of 0.782 in Clements’ test and 0.751 in the lamellar body count. Clements’ cutoff 2 with sensitivity of 67.6% and specificity of 72.2%, proved best in the prediction of the fetal lung maturity. The lamellar body count cutoff of 42x10³/μl had the sensitivity of 82.4% and specificity of 64.6% in predicting

  7. [Changes in the intensity of ultrasound echography in the fetal lung in the last trimester as a possible indication of lung maturity].

    Science.gov (United States)

    Fendel, H; Fendel, M

    1984-01-01

    The maturation of the fetal lungs that is to say the adequate production of surfactant in the fetal alveoles as it is well known, reaches to its end about the 35.-36.th week of gestation. That can be proved by the measurement of the phospholipides in the amniotic fluid L/S ratio (Gluck). In order to find signs of lung maturity by ultrasound we studied fetuses between 25-42th week of gestation. Using an oblique coronal longitudinal scan through the fetal thorax and abdomen the right hemidiaphragm and subjacent liver could be seen. With increasing fetal maturity (32.-35.th week of gestation) lung reflectivity became greater than liver reflectivity at equivalent parts of the ultrasonic beam. After the 36th week of gestation, lung reflectivity was nearly always greater than liver reflectivity as possible sign of fetal lung maturity.

  8. Molecular Determinants of Lung Development

    Science.gov (United States)

    Morrisey, Edward E.; Cardoso, Wellington V.; Lane, Robert H.; Rabinovitch, Marlene; Abman, Steven H.; Ai, Xingbin; Albertine, Kurt H.; Bland, Richard D.; Chapman, Harold A.; Checkley, William; Epstein, Jonathan A.; Kintner, Christopher R.; Kumar, Maya; Minoo, Parviz; Mariani, Thomas J.; McDonald, Donald M.; Mukouyama, Yoh-suke; Prince, Lawrence S.; Reese, Jeff; Rossant, Janet; Shi, Wei; Sun, Xin; Werb, Zena; Whitsett, Jeffrey A.; Gail, Dorothy; Blaisdell, Carol J.

    2013-01-01

    Development of the pulmonary system is essential for terrestrial life. The molecular pathways that regulate this complex process are beginning to be defined, and such knowledge is critical to our understanding of congenital and acquired lung diseases. A recent workshop was convened by the National Heart, Lung, and Blood Institute to discuss the developmental principles that regulate the formation of the pulmonary system. Emerging evidence suggests that key developmental pathways not only regulate proper formation of the pulmonary system but are also reactivated upon postnatal injury and repair and in the pathogenesis of human lung diseases. Molecular understanding of early lung development has also led to new advances in areas such as generation of lung epithelium from pluripotent stem cells. The workshop was organized into four different topics, including early lung cell fate and morphogenesis, mechanisms of lung cell differentiation, tissue interactions in lung development, and environmental impact on early lung development. Critical points were raised, including the importance of epigenetic regulation of lung gene expression, the dearth of knowledge on important mesenchymal lineages within the lung, and the interaction between the developing pulmonary and cardiovascular system. This manuscript describes the summary of the discussion along with general recommendations to overcome the gaps in knowledge in lung developmental biology. PMID:23607856

  9. Sexually dimorphic gene expression that overlaps maturation of type II pneumonocytes in fetal mouse lungs

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    Provost Pierre R

    2006-05-01

    Full Text Available Abstract Background In human, respiratory distress of the neonates, which occurs in prematurity, is prevalent in male. Late in gestation, maturation of type II pneumonocytes, and consequently the surge of surfactant synthesis are delayed in male fetuses compared with female fetuses. Although the presence of higher levels of androgens in male fetuses is thought to explain this sex difference, the identity of genes involved in lung maturation that are differentially modulated according to fetal sex is unknown. We have studied the sex difference in developing mouse lung by gene profiling during a three-day gestational window preceding and including the emergence of mature PTII cells (the surge of surfactant synthesis in the mouse occurs on GD 17.5. Methods Total RNA was extracted from lungs of male and female fetal mice (gestation days 15.5, 16.5, and 17.5, converted to cRNA, labeled with biotin, and hybridized to oligonucleotide microarrays (Affymetrix MOE430A. Analysis of data was performed using MAS5.0, LFCM and Genesis softwares. Results Many genes involved in lung maturation were expressed with no sex difference. Of the approximative 14 000 transcripts covered by the arrays, only 83 genes presented a sex difference at one or more time points between GDs 15.5 and 17.5. They include genes involved in hormone metabolism and regulation (i.e. steroidogenesis pathways, apoptosis, signal transduction, transcriptional regulation, and lipid metabolism with four apolipoprotein genes. Genes involved in immune functions and other metabolisms also displayed a sex difference. Conclusion Among these sexually dimorphic genes, some may be candidates for a role in lung maturation. Indeed, on GD 17.5, the sex difference in surfactant lipids correlates with the sex difference in pulmonary expression of apolipoprotein genes, which are involved in lipid transport. This suggests a role for these genes in the surge of surfactant synthesis. Our results would help to

  10. Role of skeletal muscle in lung development.

    Science.gov (United States)

    Baguma-Nibasheka, Mark; Gugic, Dijana; Saraga-Babic, Mirna; Kablar, Boris

    2012-07-01

    Skeletal (striated) muscle is one of the four basic tissue types, together with the epithelium, connective and nervous tissues. Lungs, on the other hand, develop from the foregut and among various cell types contain smooth, but not skeletal muscle. Therefore, during earlier stages of development, it is unlikely that skeletal muscle and lung depend on each other. However, during the later stages of development, respiratory muscle, primarily the diaphragm and the intercostal muscles, execute so called fetal breathing-like movements (FBMs), that are essential for lung growth and cell differentiation. In fact, the absence of FBMs results in pulmonary hypoplasia, the most common cause of death in the first week of human neonatal life. Most knowledge on this topic arises from in vivo experiments on larger animals and from various in vitro experiments. In the current era of mouse mutagenesis and functional genomics, it was our goal to develop a mouse model for pulmonary hypoplasia. We employed various genetically engineered mice lacking different groups of respiratory muscles or lacking all the skeletal muscle and established the criteria for pulmonary hypoplasia in mice, and therefore established a mouse model for this disease. We followed up this discovery with systematic subtractive microarray analysis approach and revealed novel functions in lung development and disease for several molecules. We believe that our approach combines elements of both in vivo and in vitro approaches and allows us to study the function of a series of molecules in the context of lung development and disease and, simultaneously, in the context of lung's dependence on skeletal muscle-executed FBMs.

  11. Effect of antenatal corticosteroid treatment on the fetal lung: a magnetic resonance imaging study.

    Science.gov (United States)

    Schmid, M; Kasprian, G; Kuessel, L; Messerschmidt, A; Brugger, P C; Prayer, D

    2011-07-01

    To investigate the effect of antenatal corticosteroid treatment on the fetal lung using magnetic resonance imaging. Prospective evaluation of 30 consecutive singleton pregnancies that received antenatal corticosteroid treatment (12 mg betamethasone i.m. on admission and 24 h later) because of threatened preterm birth. Fetal lungs were assessed using T2-weighted single-shot fast spin-echo images of a whole-body 1.5-T superconducting unit twice: less than 24 h and more than 48 h after the first course of betamethasone. Lung volumes and lung-liver signal-intensity ratios were compared between the two time points. Nine patients had to be excluded from the analysis because they did not complete the study protocol as required. Ten female and 11 male fetuses with a gestational age between 23.4 and 32.6 weeks were included in the final analysis. The mean gestational age of included fetuses was 27.5 ± 2.8 weeks. Using a linear regression model, a significant influence of gestational age on ln fetal lung volume (r(2)=0.414; P<0.0001) and lung-liver signal-intensity ratios (r(2)=0.271, P<0.0001) was found. Between the two evaluated time points, a significant increase in lung-liver signal-intensity ratios (2.34 ± 0.72 vs. 3.22 ± 1.12, P<0.0001), but not in mean lung volumes (46.6 ± 20.7 cm(3) vs. 48.8 ± 16.0 cm(3) , P=0.292), was observed. We demonstrate a significant increase in lung-liver signal-intensity ratios after antenatal corticosteroid treatment for induction of lung maturation which most likely reflects changing properties of the fetal lung parenchyma. This could potentially be useful in non-invasively assessing the effect of antenatal corticosteroid treatment on the lungs of fetuses at risk for preterm birth. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.

  12. The effects of betamethasone on allopregnanolone concentrations and brain development in preterm fetal sheep.

    Science.gov (United States)

    Yawno, Tamara; Mortale, Monique; Sutherland, Amy E; Jenkin, Graham; Wallace, Euan M; Walker, David W; Miller, Suzanne L

    2014-10-01

    The risk of preterm delivery often means that the fetus will be exposed to exogenous synthetic glucocorticoids to accelerate fetal lung maturation, but effects on other organs, particularly the brain, are not understood. The neurosteroid allopregnanolone (AP) is a GABAA receptor agonist that influences fetal brain development and has neuroprotective properties. In this study we determined the impact of maternal glucocorticoid (betamethasone) administration on brain development and AP synthesis in preterm fetal sheep. Pregnant ewes underwent surgery at 105 days gestation for implantation of fetal catheters. Ewes received either betamethasone (BM; 11.4 mg; n=10) or vehicle (saline; n=5) by i.m injection on days five (BM1) and six (BM2) following surgery. Five fetuses of the BM treated ewes received an infusion of alfaxalone (20 mg) over 48 h commencing 30 min prior to BM1. All animals were euthanased on day 7, and the fetal brains collected to determine AP concentrations and histopathology. BM significantly reduced AP levels in the fetal brain and placental cotyledons, and also in fetal plasma without altering progesterone concentrations. There was a significant decrease in the number of myelinating cells in subcortical white matter, but no change to total oligodendrocyte number. Co-administration of the AP analogue analog alfaxalone with BM prevented this change in MBP expression. BM, given at a dose clinically prescribed to accelerate lung maturation, adversely affects neurosteroid levels in the preterm fetal brain, and affects the maturational profile of white matter development; these effects were mitigated by the co-administration of alfaxolone.

  13. Thrown off balance: the effect of antenatal inflammation on the developing lung and immune system.

    Science.gov (United States)

    Kunzmann, Steffen; Collins, Jennifer J P; Kuypers, Elke; Kramer, Boris W

    2013-06-01

    In recent years, translational research with various animal models has been helpful to answer basic questions about the effect of antenatal inflammation on maturation and development of the fetal lung and immune system. The fetal lung and immune systems are very plastic and their development can be conditioned and influenced by both endogenous and/or exogenous factors. Antenatal inflammation can induce pulmonary inflammation, leading to lung injury and remodeling in the fetal lung. Exposure to antenatal inflammation can induce interleukin-1α production, which enhances surfactant protein and lipid synthesis thereby promoting lung maturation. Interleukin-1α is therefore a candidate for the link between lung inflammation and lung maturation, preventing respiratory distress syndrome in preterm infants. Antenatal inflammation can, however, cause structural changes in the fetal lung and affect the expression of growth factors, such as transforming growth factor-beta, connective tissue growth factor, fibroblast growth factor-10, or bone morphogenetic protein-4, which are essential for branching morphogenesis. These alterations cause alveolar and microvascular simplification resembling the histology of bronchopulmonary dysplasia. Antenatal inflammation may also affect neonatal outcome by modulating the responsiveness of the immune system. Lipopolysaccharide-tolerance (endotoxin hyporesponsiveness/immunoparalysis), induced by exposure to inflammation in utero, may prevent fetal lung damage, but increases susceptibility to postnatal infections. Moreover, prenatal exposure to inflammation appears to be a predisposition for the development of adverse neonatal outcomes, like bronchopulmonary dysplasia, if the preterm infant is exposed to a second postnatal hit, such as mechanical ventilation oxygen exposure, infections, or steroids.

  14. Fetal jaw movement affects condylar cartilage development.

    Science.gov (United States)

    Habib, H; Hatta, T; Udagawa, J; Zhang, L; Yoshimura, Y; Otani, H

    2005-05-01

    Using a mouse exo utero system to examine the effects of fetal jaw movement on the development of condylar cartilage, we assessed the effects of restraint of the animals' mouths from opening, by suture, at embryonic day (E)15.5. We hypothesized that pre-natal jaw movement is an important mechanical factor in endochondral bone formation of the mandibular condyle. Condylar cartilage was reduced in size, and the bone-cartilage margin was ill-defined in the sutured group at E18.5. Volume, total number of cells, and number of 5-bromo-2'-deoxyuridine-positive cells in the mesenchymal zone were lower in the sutured group than in the non-sutured group at E16.5 and E18.5. Hypertrophic chondrocytes were larger, whereas fewer apoptotic chondrocytes and osteoclasts were observed in the hypertrophic zone in the sutured group at E18.5. Analysis of our data revealed that restricted fetal TMJ movement influences the process of endochondral bone formation of condylar cartilage.

  15. Reproducible isolation of type II pneumocytes from fetal and adult rat lung using nycodenz density gradients.

    Science.gov (United States)

    Viscardi, R M; Ullsperger, S; Resau, J H

    1992-01-01

    Isolating fresh, relatively pure type II pneumocytes from the lung, particularly of fetal origin, is a difficult process. Separation by buoyant density gradient centrifugation has been used successfully to isolate adult type II cells. There is concern, however, that Percoll, a gradient medium that is commonly used for type II cell isolation, may be toxic to cells. We evaluated a new gradient medium, Nycodenz, that is (1) a true solution, (2) transparent, (3) not metabolized by cells, and (4) nontoxic to cells. Type II pneumocytes were isolated from 19- and 21-day gestation fetal and adult rat lung by elastase digestion and separated on preformed isotonic Nycodenz gradients (2 mL each of 27.6, 20.7, 13.8, and 4.6 (w/v) solutions). Type II pneumocytes were recovered from the density range 1.057-1.061 and identified by binding of FITC-conjugated and gold-complexed Maclura pomifera lectin. Cells derived from 19-day fetal lung contained abundant glycogen and reacted with a monoclonal antibody to the cytokeratins 8 and 18, which are markers of the fetal type II cell. Adult type II cells reacted with antibodies to cytokeratins 8, 18, and 19. Type II cell purity was 79.7 +/- 2.4%, 83.8 +/- 2.8%, and 82.6 +/- 1.8% (means +/- SEM) for 19- and 21-day gestation fetal and adult lung preparations, respectively. Cell viability was greater than 95%. The final cell yield for adult preparations was 17.8 +/- 2.7 x 10(6)/rat (means +/- SEM). To determine if the freshly isolated type II pneumocytes were functionally active, the incorporation of [3H]choline into phosphatidylcholine was measured. The percent saturation of phosphatidylcholine was high for both populations of freshly isolated cells. However, adult type II pneumocytes incorporated [3H]choline into phosphatidylcholine more rapidly than 21-day gestation fetal cells (5.97 x 10(-3) dpm/10(6) cells/h vs. 0.32 x 10(-3) dpm/10(6) cells/h, P less than .005). We have demonstrated that, using the Nycodenz isolation method, it is

  16. The fetal MR appearance of 'nutmeg lung': findings in 8 cases linked to pulmonary lymphangiectasia

    Energy Technology Data Exchange (ETDEWEB)

    Victoria, Teresa [The Children' s Hospital of Philadelphia, Radiology Department, Center for Fetal Diagnosis and Treatment, Philadelphia, PA (United States); Andronikou, Savvas [University of the Witwatersrand, Department of Radiology, Faculty of Health Sciences, Cape Town (South Africa)

    2014-10-15

    A pattern of abnormal signal at fetal MRI may be seen in the setting of primary or secondary congenital lymphangiectasia, manifested as a heterogeneous appearance of the lung parenchyma and the presence of subtle T2-hyperintense branching tubular structures that emanate from the hila. We have named this pattern the nutmeg lung. We describe the nutmeg lung appearance seen in fetal MRI scans, with discussion of possible etiologies and outcomes in a series of eight fetuses. We retrospectively reviewed imaging from a database of patients demonstrating features of nutmeg lung on fetal MRI. Medical records were used to determine the postnatal diagnosis, clinical course and outcome. Among the eight fetal cases of nutmeg lung, two had postnatal confirmation of primary lymphangiectasia and the remaining six had secondary lymphangiectasia, presumably secondary to congenital cardiac anomalies. There were various-size pleural effusions in all cases. Only one of the cases demonstrated hydrops fetalis. We present the description of the nutmeg lung sign on fetal MRI as T2-hyperintense heterogeneous lungs with fluid-filled, serpiginous branching structures that extend from the pulmonary hila to the periphery of the lung, often accompanied by pleural effusions. The sign denotes findings of primary or secondary lymphangiectasia. Findings of secondary lymphangiectasia in our series were a result of cardiac insufficiency. Recognizing this sign might be helpful in the diagnostic algorithm of the fetus with abnormal lung parenchyma. (orig.)

  17. TEMPORAL EXPRESSION OF NOTCH RECEPTORS DURING LUNG DEVELOPMENT IN RAT

    Institute of Scientific and Technical Information of China (English)

    ZHANG Qian-shen; CHANG Li-wen; LIU Han-chu; RONG Zhi-hu; CHEN Hong-bing

    2005-01-01

    Objective To investigate the temporal expression of Notch receptors in developing lungs of rats and to explore the regulating role of Notch in lung development. Methods We studied the expression of Notch1,2,3 isforms in embryonic days 18,20,21 and postnatal days 1,4,7,14, 21 rat lungs. Six rats of each group were used to assess lung histologic changes by HE staining and expression of Notch in lungs by immunohistochemistry. Total RNA was extracted by Trizol reagent from the frozen lung tissues. mRNA levels of Notch were measured by reverse transcription polymerase chain reaction (RT-PCR). Results It is showed that Notch1-3 mainly localized in the airway surface epithelium、alveolar epithelium during the psdueoglandular stage, and reached the peaks at canalicular period. The expression patterns of Notch1-3 were changed with the fetal age. Conclusion These results support multiple roles for Notch1,2,and 3 receptor activation during lung development, probably not only modulating the process of branching morphogenesis but also involved in determining the cell differentiation fate in fetal alveolar epithelium.

  18. The Effects of Fetal Surgery on Retinopathy of Prematurity Development

    Directory of Open Access Journals (Sweden)

    Sudha Nallasamy

    2009-10-01

    Full Text Available Background: Fetal surgery is selectively offered for severe or life-threatening fetal malformations. These infants are often born prematurely and are thus at risk for retinopathy of prematurity (ROP. It is not known whether fetal surgery confers an increased risk of developing severe ROP relative to published rates in standard premature populations ≤37 weeks of age grouped by birth weight (

  19. Decreased fetal movements at home were recorded by a newly developed fetal movement recorder in a case of a non-reassuring fetal status.

    Science.gov (United States)

    Ryo, Eiji; Kamata, Hideo; Seto, Michiharu

    2014-10-01

    A fetal movement acceleration measurement (FMAM) recorder was developed for home monitoring of fetal movements. We provided a 32-year-old pregnant woman with the FMAM recorder to home monitor fetal movements, thereby self-recording decreased fetal movements at 30 weeks' gestation. On routine checkup, a non-stress test revealed scant fetal heart rate accelerations. At 31 weeks' gestation, the woman underwent an emergent caesarean delivery because of a non-reassuring fetal heart rate pattern, and delivered a female neonate weighing 1312 g, whose umbilical cord was slightly narrowed at the umbilicus. Our experience with the present case suggests the usefulness of the FMAM recorder.

  20. Childhood cognitive development after fetal growth restriction.

    Science.gov (United States)

    Llurba, E; Baschat, A A; Turan, O M; Harding, J; McCowan, L M

    2013-04-01

    To examine the relationship between prenatal umbilical artery (UA) and internal carotid artery (ICA) Doppler findings and cognitive development at 3 and 6 years in low-birth-weight children. This was a study of 209 low-birth-weight (Cognitive ability at 3 and 6 years' corrected age was assessed using the fourth edition of the Stanford-Binet Intelligence Scale (SBIS) and compared between SGA and FGR groups. An SBIS score development. The median gestational age at diagnosis of abnormal fetal growth was 36.6 (range, 28-41) weeks. There were 87 (41.6%) children classified as having FGR and 122 (58.4%) as SGA. The mean global SBIS score at 3 years was 109.4 (SD, 22.8) and at 6 years it was 110.5 (SD, 13.9). Overall, 22 (10.5%) children had delayed development at 3 years. Total SBIS scores and individual domain scores did not differ between FGR and SGA groups at 3 or 6 years and similar proportions in each group had delayed development. Abnormal prenatal UA and ICA Doppler findings are not associated with lower developmental scores in low-birth-weight children delivered in the third trimester of pregnancy. Copyright © 2013 ISUOG. Published by John Wiley & Sons, Ltd.

  1. Validity of lamellar body count as a fetal lung maturity assessment in twin pregnancy.

    Science.gov (United States)

    Tsuda, Hiroyuki; Kotani, Tomomi; Sumigama, Seiji; Kawabata, Ichiro; Takahashi, Yuichiro; Iwagaki, Shigenori; Kigoshi, Kaori; Kikkawa, Fumitaka

    2012-08-01

    Fetal lung maturity assessment in twin pregnancy has been discussed, but is still controversial. The purpose of this study is to predict the occurrence of respiratory distress syndrome (RDS) using lamellar body count (LBC) and analyze the validity of LBC for fetal lung maturity assessment in twin pregnancy. Three-hundred two amniotic fluid samples were obtained at cesarean section from 29 to 38 weeks of gestation. Samples were analyzed immediately with no centrifugation and the number of lamellar bodies was counted using a platelet channel on the Sysmex SF-3000. There were 18 neonates (6.0%) suffering from RDS. An LBC cut-off value of 2.95×10⁴/μL resulted in 91.5% sensitivity and 83.3% specificity for predicting RDS. This cut-off value for predicting RDS was the same as that in singleton pregnancy. Moreover, the median LBC value in RDS cases was significantly lower than in non-RDS cases (1.50±1.1×10⁴/μL vs. 10.6±7.5×10⁴/μL; ptwin pregnancy and also the largest study on fetal lung maturity assessment in twin pregnancy. An LBC value of >2.95×10⁴/μL means reassuring findings for RDS even in twin pregnancy. We believe the data in this study provide valuable, new information for the management of twin pregnancies.

  2. The importance of thyroid hormone sulfation during fetal development

    NARCIS (Netherlands)

    M.H.A. Kester (Monique)

    2001-01-01

    textabstractNormal fetal development requires the presence of thyroid hormone. Disruption of any of the processes regulating the bioavailability of thyroid hormone may contribute to congenital anomalies. This thesis is focussed a) on the importance of thyroid hormone sulfation during fetal developme

  3. Atlas learning in fetal brain development.

    Science.gov (United States)

    Dittrich, Eva; Kasprian, Gregor; Prayer, Daniela; Langs, Georg

    2011-06-01

    Magnetic resonance imaging has become an important noninvasive technique to gain insight into fetal brain development. Its capabilities go beyond ultrasound when diagnosing high-risk pregnancies. To summarize observations across a population in magnetic resonance imaging studies, reference systems such as atlases that establish correspondences across a cohort are key. In this article, we review the evolution of atlas-building methods in light of their relevance, limitations, and benefits for the modeling of human brain development. Starting with single anatomical templates to which brain scans where mapped to such as Talairach and Montreal Neurological Institute space, we explore the uses of atlases as a means to establish correspondences across a cohort and as a model that captures the population characteristics of the cases the atlas is built from. We discuss methods that capture features of increasingly heterogeneous populations and approaches that are able to generalize with only minimal annotation. The main focus of this review are methods that explicitly model the variability in the population with regard to time, such as in the modeling of disease progression and brain development. We highlight the applicability and limitations of state-of-the art approaches, how insights from the study of disease progression are helpful in developmental studies, and point to the directions of future research that is still necessary.

  4. Leptin promotes fetal lung maturity and upregulates SP-A expression in pulmonary alveoli type-II epithelial cells involving TTF-1 activation

    National Research Council Canada - National Science Library

    Chen, Hui; Zhang, Jian-Ping; Huang, Hui; Wang, Zhen-Hua; Cheng, Rui; Cai, Wei-Bin

    2013-01-01

    .... In the present study, we found that antenatal treatment with leptin for 2 d significantly enhanced the relative alveolus area and improved the maturity of fetal lungs in a rat model of fetal growth restriction (FGR...

  5. Mechanical properties of isolated fetal miniature pig lungs after substitution with fluorocarbons.

    Science.gov (United States)

    Widjaja, B; Wuthe, J; Schmidt, A; Seitz, B; Rüfer, R

    1988-01-01

    In our present study we tried to inflate and stabilize isolated immature lungs of fetal minipigs in gestation age of 95 days (= 85% of total normal gestation period) with different fluorocarbons. Based on our previous experiences, the immature lungs at day 95 are almost non inflatable with air. For our experiments we used fluorocarbon 43 (FC-43) with a surface tension of 16 mN/m and fluorocarbon 72 (FC-72) with a surface tension of 12 mN/m. Eighteen fetal immature lungs were used. In group 1 the lungs were rinsed with FC-43; in group 2 the rinse solution was FC-72, and in group 3 the lungs were untreated. After removing the fluorocarbon, in the case of groups 1 and 2, the lungs were artificially ventilated. Pressure-volume (p-v) curves were registered in the beginning (immediately after FC lavage), after 10 and 20 min of artificial ventilation. Airway opening pressure (pi) and weight-specific end-inspiratory lung compliance (ci) were investigated. Statistically significant differences in weight-specific end-inspiratory compliance were found between FC groups and untreated group 3, but no stabilization could be seen during the investigation period of 20 min. No statistically significant improvement in weight-specific end-inspiratory compliance was observed between group 1 and 2, although the compliances of group 2 with FC-72 were better than those of group 1 with FC-43 in three p-v diagrams registered in the beginning and after 10 and 20 min of artificial ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Presenilin-1 processing of ErbB4 in fetal type II cells is necessary for control of fetal lung maturation.

    Science.gov (United States)

    Hoeing, Kristina; Zscheppang, Katja; Mujahid, Sana; Murray, Sandy; Volpe, MaryAnn V; Dammann, Christiane E L; Nielsen, Heber C

    2011-03-01

    Maturation of pulmonary fetal type II cells to initiate adequate surfactant production is crucial for postnatal respiratory function. Little is known about specific mechanisms of signal transduction controlling type II cell maturation. The ErbB4 receptor and its ligand neuregulin (NRG) are critical for lung development. ErbB4 is cleaved at the cell membrane by the γ-secretase enzyme complex whose active component is either presenilin-1 (PSEN-1) or presenilin-2. ErbB4 cleavage releases the 80kDa intracellular domain (4ICD), which associates with chaperone proteins such as YAP (Yes-associated protein) and translocates to the nucleus to regulate gene expression. We hypothesized that PSEN-1 and YAP have a development-specific expression in fetal type II cells and are important for ErbB4 signaling in surfactant production. In primary fetal mouse E16, E17, and E18 type II cells, PSEN-1 and YAP expression increased at E17 and E18 over E16. Subcellular fractionation showed a strong cytosolic and a weaker membrane location of both PSEN-1 and YAP. This was enhanced by NRG stimulation. Co-immunoprecipitations showed ErbB4 associated separately with PSEN-1 and with YAP. Their association, phosphorylation, and co-localization were induced by NRG. Confocal immunofluorescence and nuclear fractionation confirmed these associations in a time-dependent manner after NRG stimulation. Primary ErbB4-deleted E17 type II cells were transfected with a mutant ErbB4 lacking the γ-secretase binding site. When compared to transfection with wild-type ErbB4, the stimulatory effect of NRG on surfactant protein mRNA expression was lost. We conclude that PSEN-1 and YAP have crucial roles in ErbB4 signal transduction during type II cell maturation. Copyright © 2010 Elsevier B.V. All rights reserved.

  7. Fetal alcohol exposure and development of the integument

    Directory of Open Access Journals (Sweden)

    Longhurst WD

    2016-05-01

    Full Text Available William D Longhurst,1 Jordan Ernst,2 Larry Burd3 1Center for Emergency Medicine, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH, USA; 2University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, USA; 3Department of Pediatrics, North Dakota Fetal Alcohol Syndrome Center, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, USA Background: The physiology of fetal alcohol exposure changes across gestation. Early in pregnancy placental, fetal, and amniotic fluid concentrations of alcohol exposure are equivalent. Beginning in mid-pregnancy, the maturing fetal epidermis adds keratins which decrease permeability resulting in development of a barrier between fetal circulation and the amniotic fluid. Barrier function development is essential for viability in late pregnancy and in the extra-uterine environment. In this paper we provide a selected review of the effects of barrier function on fetal alcohol exposure. Methods: We utilized a search of PubMed and Google for all years in all languages for MeSH on Demand terms: alcohol drinking, amnion, amniotic fluid, epidermis, ethanol, female, fetal development, fetus, humans, keratins, permeability, and pregnancy. We also reviewed the reference lists of relevant papers and hand-searched reference lists of textbooks for additional references. Results: By 30 gestational weeks, development of barrier function alters the pathophysiology of ethanol dispersion between the fetus and amniotic fluid. Firstly, increases in the effectiveness of barrier function decreases the rate of diffusion of alcohol from fetal circulation across fetal skin into the amniotic fluid. This reduces the volume of alcohol entering the amniotic fluid. Secondly, barrier function increases the duration of fetal exposure by decreasing the rate of alcohol diffusion from amniotic fluid back into fetal circulation. Ethanol is then transported into

  8. Diffusion-weighted MR imaging of fetal lung maturation in sheep: effect of prenatal cortisone administration on ADC values.

    Science.gov (United States)

    Much, Chressen Catharina; Schoennagel, Björn Phillip; Yamamura, Jin; Buchert, Ralph; Kooijman, Hendrik; Schätzle, Anne-Kathrin; Adam, Gerhard; Wedegaertner, Ulrike

    2013-07-01

    To assess changes in diffusion properties in the fetal lung after cortisone administration with diffusion-weighted imaging (DWI) in fetal sheep. DWI was performed on 11 pregnant sheep with singleton pregnancies on a 1.5-T MRI scanner. Four animals received cortisone injections before baseline imaging. Seven animals served as controls. Apparent diffusion coefficient (ADC) was measured on DWI in the fetal lungs by two independent readers. The Pearson test was used to correlate ADC and gestational age. A t-test was performed to compare differences in ADC values at the baseline and follow-up images within and between groups. Inter-rater reliability was calculated. In the cortisone group, ADC values increased about 10 % between the baseline and follow-up images (P = 0.039). Comparing the cortisone and control groups, ADC values of the baseline images did not differ; whereas in the follow-up imaging, ADC values were significantly higher in the cortisone group (P = 0.024). Lung ADC values did not correlate with gestational age (P = 0.970). Inter-rater reliability was high (0.970, P = 0.000). In this experimental model, MR-DWI can detect cortisone-induced changes in diffusion properties of the fetal lung. • Corticosteroids are frequently administered antenatally to prevent fetal lung immaturity at birth • DWI can detect changes in the fetal lung after corticosteroid administration • Changes can be detected as early as 5 days after treatment • Fetal MRI may offer a non-invasive method of monitoring lung maturation.

  9. Thyroid hormone metabolism and the developing human lung.

    Science.gov (United States)

    Hume, R; Richard, K; Kaptein, E; Stanley, E L; Visser, T J; Coughtrie, M W

    2001-05-01

    Thyroid hormones are involved in the regulation of fetal lung development, and maturation is accelerated in animal models by antepartum exposure to raised concentrations of the receptor-active thyroid hormone triiodothyronine and glucocorticoids. It is essential that the nature of the regulation of the spatial and temporal metabolism of iodothyronines in the human fetus and infant is known before effective therapies can be developed to modify human lung maturation. Thyroid hormone bioavailability to the human fetus is regulated in part by enzymatic deiodination and reversible sulfation of iodothyronines, with contributions from other factors such as fetomaternal and fetoamniotic hormone transfers, fetal thyroid gland production, and the activities of plasma membrane transporters mediating uptake of iodothyronines from plasma into tissues. Copyright 2001 S. Karger AG, Basel.

  10. Fluoxetine effect on gestation and fetal development

    Directory of Open Access Journals (Sweden)

    Ösz Bianca Eugenia

    2014-08-01

    Full Text Available The prenatal exposure to selective serotonin reuptake inhibitors (SSRIs is very controversial. There is no conclusive evidence for increased risk of malformations after SSRI use in pregnancy. The aim of the study was to determine how fluoxetine is affecting gestation and fetal development in rats. Twenty sexually mature female Wistar rats weighting between 250-260 g received 20 mg/kg body weight fluoxetine from the first day of gestation and during the entire gestation period.The drug was administered by oral route. Healthy, primipareus animals were selected along with 20 female Wistar rats, as control group. Mature males were caged with virgin females for an entire week. Rat’s behaviour during gestation, after birth and rats body weight was examined. The number of healthy pups was also noted. The females not giving birth after 21 days to any pup were anesthetized (halothane through gas scavenging apparatus untilled death and the gravid uterus were dissected out and examined. Compared to the controlled group, in which weight gain was more significant, the animals from the experimental group had a slight increase in body weight. The weight gain normally induced by gestation, is less significant in fluoxetine treated rats due to the increase serotonin levels in the brain. The uteri examination of pregnant rats showed an increase in the number of dead and resorbed rat embryos. Preclinical studies suggest that the inclusion of fluoxetine in pregnancy category C is justified and the appropriateness of its administration in pregnancy is still an unresolved issue.

  11. Stimulation of MAP kinase pathways after maternal IL-1β exposure induces fetal lung fluid absorption in guinea pigs

    Directory of Open Access Journals (Sweden)

    Carter Ethan P

    2007-03-01

    Full Text Available Abstract Background We tested the hypothesis that maternal interleukin-1β (IL-1β pretreatment and induction of fetal cortisol synthesis activates MAP kinases and thereby affects lung fluid absorption in preterm guinea pigs. Methods IL-1β was administered subcutaneously daily to timed-pregnant guinea pigs for three days. Fetuses were obtained by abdominal hysterotomy and instilled with isosmolar 5% albumin into the lungs and lung fluid movement was measured over 1 h by mass balance. MAP kinase expression was measured by western blot. Results Lung fluid absorption was induced at 61 days (D gestation and stimulated at 68D gestation by IL-1β. Maternal IL-1β pretreatment upregulated ERK and upstream MEK expression at both 61 and 68D gestation, albeit being much more pronounced at 61D gestation. U0126 instillation completely blocked IL-1β-induced lung fluid absorption as well as IL-1β-induced/stimulated ERK expression. Cortisol synthesis inhibition by metyrapone attenuated ERK expression and lung fluid absorption in IL-1β-pretreated fetal lungs. JNK expression after maternal IL-1β pretreatment remained unaffected at either gestation age. Conclusion These data implicate the ERK MAP kinase pathway as being important for IL-1β induction/stimulation of lung fluid absorption in fetal guinea pigs.

  12. Stimulation of MAP kinase pathways after maternal IL-1beta exposure induces fetal lung fluid absorption in guinea pigs.

    Science.gov (United States)

    Bhattacharjee, Reshma; Li, Tianbo; Koshy, Shyny; Beard, LaMonta L; Sharma, Kapil; Carter, Ethan P; Garat, Chrystelle; Folkesson, Hans G

    2007-03-26

    We tested the hypothesis that maternal interleukin-1beta (IL-1beta) pretreatment and induction of fetal cortisol synthesis activates MAP kinases and thereby affects lung fluid absorption in preterm guinea pigs. IL-1beta was administered subcutaneously daily to timed-pregnant guinea pigs for three days. Fetuses were obtained by abdominal hysterotomy and instilled with isosmolar 5% albumin into the lungs and lung fluid movement was measured over 1 h by mass balance. MAP kinase expression was measured by western blot. Lung fluid absorption was induced at 61 days (D) gestation and stimulated at 68D gestation by IL-1beta. Maternal IL-1beta pretreatment upregulated ERK and upstream MEK expression at both 61 and 68D gestation, albeit being much more pronounced at 61D gestation. U0126 instillation completely blocked IL-1beta-induced lung fluid absorption as well as IL-1beta-induced/stimulated ERK expression. Cortisol synthesis inhibition by metyrapone attenuated ERK expression and lung fluid absorption in IL-1beta-pretreated fetal lungs. JNK expression after maternal IL-1beta pretreatment remained unaffected at either gestation age. These data implicate the ERK MAP kinase pathway as being important for IL-1beta induction/stimulation of lung fluid absorption in fetal guinea pigs.

  13. Normal renal development investigated with fetal MRI

    Energy Technology Data Exchange (ETDEWEB)

    Witzani, Linde [Department of Radiology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria)]. E-mail: linde.witzani@aon.at; Brugger, Peter Christian [Center of Anatomy and Cell Biology, Integrative Morphology Group, Medical University of Vienna, Waehringerstrasse 13, A-1090 Vienna (Austria); Hoermann, Marcus [Department of Radiology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Kasprian, Gregor [Department of Radiology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Csapone-Balassy, Csilla [Department of Radiology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Prayer, Daniela [Department of Radiology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria)

    2006-02-15

    Objective: To evaluate age-dependent changes in fetal kidney measurements with MRI. Patients and methods: Fetal MRI examinations were used to study the kidney length (218 fetuses), signal intensities of renal tissue, renal pelvis, and liver tissue on T2-weighted images (223 fetuses), and the whole-kidney apparent diffusion coefficient (107 fetuses). A 1.5 T superconducting unit with a phased array coil was used in patients from 16 to 39 weeks' gestation. The imaging protocol included T2-weighted single-shot fast spin-echo, T2-weighted balanced angiography and diffusion-weighted sequences. Slice thickness ranged from 3 to 5 mm. Results: Fetal kidney length as a function of gestational age was expressed by the linear regression: kidney length (mm) = 0.190 x gestational age (d) - 8.034 (R {sup 2} 0.883, p < 0.001). Paired t-test analysis showed a highly statistically significant difference between the ratio of renal tissue signal intensity to renal pelvis signal intensity and the ratio of liver signal intensity to renal pelvis signal intensity on T2-weighted images (t = -50.963, d.f. = 162, p < 0.001), with renal tissue hyperintense to liver tissue. The apparent diffusion coefficient in relation to gestational age was described by the equation: ADC ({mu}m{sup 2}/s) = 0.0302 x square (gestational age (d)) - 14.202 x gestational age (d) + 2728.6 (R {sup 2} = 0.225, p < 0.001). Conclusion: The length, signal intensity on T2-weighted images, and apparent diffusion coefficient of the fetal kidney change significantly with gestational age. The presented data may help in the prenatal diagnosis of renal anomalies.

  14. Normal renal development investigated with fetal MRI.

    Science.gov (United States)

    Witzani, Linde; Brugger, Peter Christian; Hörmann, Marcus; Kasprian, Gregor; Csapone-Balassy, Csilla; Prayer, Daniela

    2006-02-01

    To evaluate age-dependent changes in fetal kidney measurements with MRI. Fetal MRI examinations were used to study the kidney length (218 fetuses), signal intensities of renal tissue, renal pelvis, and liver tissue on T2-weighted images (223 fetuses), and the whole-kidney apparent diffusion coefficient (107 fetuses). A 1.5 T superconducting unit with a phased array coil was used in patients from 16 to 39 weeks' gestation. The imaging protocol included T2-weighted single-shot fast spin-echo, T2-weighted balanced angiography and diffusion-weighted sequences. Slice thickness ranged from 3 to 5mm. Fetal kidney length as a function of gestational age was expressed by the linear regression: kidney length (mm)=0.190 x gestational age (d) -8.034 (R(2) = 0.883, p < 0.001). Paired t-test analysis showed a highly statistically significant difference between the ratio of renal tissue signal intensity to renal pelvis signal intensity and the ratio of liver signal intensity to renal pelvis signal intensity on T2-weighted images (t = -50.963, d.f. = 162, p < 0.001), with renal tissue hyperintense to liver tissue. The apparent diffusion coefficient in relation to gestational age was described by the equation: ADC (microm(2)/s) = 0.0302 x square (gestational age (d)) -14.202 x gestational age (d) +2,728.6 (R(2) = 0.225, p < 0.001). The length, signal intensity on T2-weighted images, and apparent diffusion coefficient of the fetal kidney change significantly with gestational age. The presented data may help in the prenatal diagnosis of renal anomalies.

  15. Distending Pressure Did Not Activate Acute Phase or Inflammatory Responses in the Airways and Lungs of Fetal, Preterm Lambs.

    Directory of Open Access Journals (Sweden)

    Rebecca Y Petersen

    Full Text Available Mechanical ventilation at birth causes airway injury and lung inflammation in preterm sheep. Continuous positive airway pressure (CPAP is being increasingly used clinically to transition preterm infants at birth.To test if distending pressures will activate acute phase reactants and inflammatory changes in the airways of fetal, preterm lambs.The head and chest of fetal lambs at 128±1 day GA were surgically exteriorized. With placental circulation intact, fetal lambs were then randomized to one of five 15 minute interventions: PEEP of 0, 4, 8, 12, or 16 cmH2O. Recruitment volumes were recorded. Fetal lambs remained on placental support for 30 min after the intervention. The twins of each 0 cmH2O animal served as controls. Fetal lung fluid (FLF, bronchoalveolar lavage fluid (BAL, right mainstem bronchi and peripheral lung tissue were evaluated for inflammation.Recruitment volume increased from 0.4±0.04 mL/kg at 4 cmH2O to 2.4±0.3 mL/kg at 16 cmH2O. The lambs were surfactant deficient, and all pressures were below the opening inflection pressure on pressure-volume curve. mRNA expression of early response genes and pro-inflammatory cytokines did not increase in airway tissue or lung tissue at any pressure compared to controls. FLF and BAL also did not have increases in early response proteins. No histologic changes or Egr-1 activation was present at the pressures used.Distending pressures as high as 16 cmH2O did not recruit lung volume at birth and did not increase markers of injury in the lung or airways in non-breathing preterm fetal sheep.

  16. Sustained inflation at birth did not alter lung injury from mechanical ventilation in surfactant-treated fetal lambs.

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    Noah H Hillman

    Full Text Available BACKGROUND: Sustained inflations (SI are used with the initiation of ventilation at birth to rapidly recruit functional residual capacity and may decrease lung injury and the need for mechanical ventilation in preterm infants. However, a 20 second SI in surfactant-deficient preterm lambs caused an acute phase injury response without decreasing lung injury from subsequent mechanical ventilation. HYPOTHESIS: A 20 second SI at birth will decrease lung injury from mechanical ventilation in surfactant-treated preterm fetal lambs. METHODS: The head and chest of fetal sheep at 126±1 day GA were exteriorized, with tracheostomy and removal of fetal lung fluid prior to treatment with surfactant (300 mg in 15 ml saline. Fetal lambs were randomized to one of four 15 minute interventions: 1 PEEP 8 cmH2O; 2 20 sec SI at 40 cmH2O, then PEEP 8 cmH2O; 3 mechanical ventilation with 7 ml/kg tidal volume; or 4 20 sec SI then mechanical ventilation at 7 ml/kg. Fetal lambs remained on placental support for the intervention and for 30 min after the intervention. RESULTS: SI recruited a mean volume of 6.8±0.8 mL/kg. SI did not alter respiratory physiology during mechanical ventilation. Heat shock protein (HSP 70, HSP60, and total protein in lung fluid similarly increased in both ventilation groups. Modest pro-inflammatory cytokine and acute phase responses, with or without SI, were similar with ventilation. SI alone did not increase markers of injury. CONCLUSION: In surfactant treated fetal lambs, a 20 sec SI did not alter ventilation physiology or markers of lung injury from mechanical ventilation.

  17. Slit and robo expression in the developing mouse lung.

    Science.gov (United States)

    Greenberg, James M; Thompson, Felisa Y; Brooks, Sherry K; Shannon, John M; Akeson, Ann L

    2004-06-01

    Mammalian lung development is mediated through complex interactions between foregut endoderm and surrounding mesenchyme. As airway branching progresses, the mesenchyme undergoes dramatic remodeling and differentiation. Little is understood about the mechanisms that direct mesenchymal organization during lung development. A screen for candidate genes mediating this process identified Slit, a ligand for the Roundabout (Robo) receptor previously associated with guidance of axonal projections during central nervous system development. Here, we demonstrate by in situ hybridization that two Slit genes (Slit-2 and Slit-3) and two Robo genes (Robo-1 and Robo-2) are expressed in fetal lung mesenchyme. Slit-2 and Robo-1 expression is present throughout mesenchyme at midgestation and is not detectable by newborn day 1. Slit-3 and Robo-2 expression is restricted to specific, complementary subsets of mesenchyme. Robo-2 is expressed in mesenchymal cells immediately adjacent to large airways, whereas Slit-3 expression predominates in mesenchyme remote from airway epithelium. The temporal and spatial distribution of Slit and Robo mRNAs indicate that these genes may direct the functional organization and differentiation of fetal lung mesenchyme.

  18. Effect of hyperoxia on the airway and vascular development in fetal lung and the intervention of dexamethasone%高氧对胎儿肺气道及血管发育的影响及地塞米松的干预作用

    Institute of Scientific and Technical Information of China (English)

    李娟; 刘博

    2008-01-01

    目的 探讨高氧对人胎儿肺泡及肺血管发育的影响及地塞米松的干预作用.方法 假腺体期胎儿肺组织分别于高氧(95 96O2,5%CO2)及正常氧(21%O2,5%CO2)中培养72 h,两组又分别同时加入地塞米松(10-6mol/L),对照组以相同浓度乙醇代替.收获的肺组织分别以细胞角蛋白和CD31确定上皮细胞及内皮细胞,用图像分析系统计算出气道厚度、气道占组织百分比、血管距最近气道距离、血管占间质比例.结果 空气培养72 h,肺结构与新鲜肺组织比较无明显变化;高氧组气道明显扩张.上皮明显变薄,气道所占比例明显增加(P<0.05).高氧组肺间质毛细血管明显靠近气道(50μm),该组血管所占面积(4.0%)明显小于正常氧(4.2%)和高氧+地塞米松组(5.4%)(P<0.05).地塞米松可抑制高氧对肺组织的不良效应.结论 高氧导致胎儿肺组织气道简单化及间质血管减少;地塞米松可阻止这些变化,促进肺成熟.%Objective To investigate the effects of dexamethasone on the airway development and vasculogenesis in cultured human fetal lung exposed to hyperoxia.Methods Human fetal lung at the pseudoglandular stage of development were cultured either in normoxia(21%O2,5%CO2)or hyperoxia(95%O2,5% CO2)for 72 hours.Dexamethasone was added into the culture medium at the concentration of 10-6 mol/L.Whereas ethanol at the same concentration was as control.Harvested tissue wss stained for pancytokeratin to I dentify epithelial cells.CD31 aS a specific antibody of endothelial cell.The effects of lung morphometry were analyzed using computer-assisted image analysis software to ealeuhte the thickness of airways,surface area occupied by airways and the distance of vessels to the nearest airway as well as the surface area of blood vessels.Results The lung architecture remained largely unchanged in normoxia for 72 hours culture,whereas hyperoxic culture of lungs resulted in significant dilation of airways and thinning of

  19. Blood borne: bacterial components in mother's blood influence fetal development.

    Science.gov (United States)

    Loughran, Allister J; Tuomanen, Elaine I

    2016-01-01

    Bacterial or viral infection of the mother during the course of pregnancy can cross the placenta and actively infect the fetus. However, especially for bacteria, it is more common for mothers to experience an infection that can be treated without overt fetal infection. In this setting, it is less well understood what the risk to fetal development is, particularly in terms of neurological development. This research highlight reviews recent findings indicating that bacterial components generated during infection of the mother can cross the placenta and activate the fetal innate immune system resulting in changes in the course of brain development and subsequent progression to postnatal cognitive disorders. Bacterial cell wall is a ubiquitous bacterial PAMP (pathogen-associated molecular pattern) known to activate inflammation through the stimulation of TLR2. Cell wall is released from bacteria during antibiotic treatment and new work shows that embryos exposed to cell wall from the mother demonstrate anomalous proliferation of neuronal precursor cells in a TLR2 dependent manner. Such proliferation increases the neuronal density of the cortical plate and alters brain architecture. Although there is no fetal death, subsequent cognitive development is significantly impaired. This model system suggests that bacterial infection of the mother and its treatment can impact fetal brain development and requires greater understanding to potentially eliminate a risk factor for cognitive disorders such as autism.

  20. Perinatal Maternal Mental Health, Fetal Programming and Child Development.

    Science.gov (United States)

    Lewis, Andrew J; Austin, Emma; Knapp, Rebecca; Vaiano, Tina; Galbally, Megan

    2015-11-26

    Maternal mental disorders over pregnancy show a clear influence on child development. This review is focused on the possible mechanisms by which maternal mental disorders influence fetal development via programming effects. This field is complex since mental health symptoms during pregnancy vary in type, timing and severity and maternal psychological distress is often accompanied by higher rates of smoking, alcohol use, poor diet and lifestyle. Studies are now beginning to examine fetal programming mechanisms, originally identified within the DOHaD framework, to examine how maternal mental disorders impact fetal development. Such mechanisms include hormonal priming effects such as elevated maternal glucocorticoids, alteration of placental function and perfusion, and epigenetic mechanisms. To date, mostly high prevalence mental disorders such as depression and anxiety have been investigated, but few studies employ diagnostic measures, and there is very little research examining the impact of maternal mental disorders such as schizophrenia, bipolar disorder, eating disorders and personality disorders on fetal development. The next wave of longitudinal studies need to focus on specific hypotheses driven by plausible biological mechanisms for fetal programming and follow children for a sufficient period in order to examine the early manifestations of developmental vulnerability. Intervention studies can then be targeted to altering these mechanisms of intergenerational transmission once identified.

  1. Perinatal Maternal Mental Health, Fetal Programming and Child Development

    Directory of Open Access Journals (Sweden)

    Andrew J. Lewis

    2015-11-01

    Full Text Available Maternal mental disorders over pregnancy show a clear influence on child development. This review is focused on the possible mechanisms by which maternal mental disorders influence fetal development via programming effects. This field is complex since mental health symptoms during pregnancy vary in type, timing and severity and maternal psychological distress is often accompanied by higher rates of smoking, alcohol use, poor diet and lifestyle. Studies are now beginning to examine fetal programming mechanisms, originally identified within the DOHaD framework, to examine how maternal mental disorders impact fetal development. Such mechanisms include hormonal priming effects such as elevated maternal glucocorticoids, alteration of placental function and perfusion, and epigenetic mechanisms. To date, mostly high prevalence mental disorders such as depression and anxiety have been investigated, but few studies employ diagnostic measures, and there is very little research examining the impact of maternal mental disorders such as schizophrenia, bipolar disorder, eating disorders and personality disorders on fetal development. The next wave of longitudinal studies need to focus on specific hypotheses driven by plausible biological mechanisms for fetal programming and follow children for a sufficient period in order to examine the early manifestations of developmental vulnerability. Intervention studies can then be targeted to altering these mechanisms of intergenerational transmission once identified.

  2. Dihydrotestosterone Potentiates EGF-Induced ERK Activation by Inducing SRC in Fetal Lung Fibroblasts

    Science.gov (United States)

    Smith, Susan M.; Murray, Sandy; Pham, Lucia D.; Minoo, Parviz; Nielsen, Heber C.

    2014-01-01

    Lung maturation is regulated by interactions between mesenchymal and epithelial cells, and is delayed by androgens. Fibroblast–Type II cell communications are dependent on extracellular signal-regulated kinases (ERK) 1/2 activation by the ErbB receptor ligands epidermal growth factor (EGF), transforming growth factor (TGF)-α, and neuregulin (Nrg). In other tissues, dihydrotestosterone (DHT) has been shown to activate SRC by a novel nontranscriptional mechanism, which phosphorylates EGF receptors to potentiate EGF-induced ERK1/2 activation. This study sought to determine if DHT potentiates EGFR signaling by a nontranscriptional mechanism. Embryonic day (E)17 fetal lung cells were isolated from dams treated with or without DHT since E12. Cells were exposed to 30 ng/ml DHT for periods of 30 minutes to 3 days before being stimulated with 100 ng/ml EGF, TGF-α, or Nrg for up to 30 minutes. Lysates were immunoblotted for ErbB and SRC pathway signaling intermediates. DHT increased ERK1/2 activation by EGF, TGF-α, and Nrg in fibroblasts and Type II cells. Characterization in fibroblasts showed that potentiation of the EGF pathway was significant after 60 minutes of DHT exposure and persisted in the presence of the translational inhibitor cycloheximide. SRC and EGF receptor phosphorylation was increased by DHT, as was EGF-induced SHC1 phosphorylation and subsequent association with GRB2. Finally, SRC silencing, SRC inhibition with PP2, and overexpression of a dominant-negative SRC each prevented DHT from increasing EGF-induced ERK1/2 phosphorylation. These results suggest that DHT activates SRC to potentiate the signaling pathway leading from the EGF receptor to ERK activation in primary fetal lung fibroblasts. PMID:24484548

  3. Macro- and micromineral composition of fetal pigs and their accretion rates during fetal development.

    Science.gov (United States)

    Mahan, D C; Watts, M R; St-Pierre, N

    2009-09-01

    Twenty-six crossbreed (Yorkshire x Landrace) sows bred to Duroc boars were used to determine fetal measurements and mineral compositions at various stages of gestation. Sows were fed a vitamin and mineral fortified 15% CP corn soybean meal gestation diet fed at 2.1 kg daily with dietary minerals meeting or in excess of NRC requirements. Sow and litter measurements were evaluated at 5 periods postcoitum (45, 62, 80, 100, 115 d). The experiment was conducted as a completely randomized design with 3 to 6 observations per mean. Uterine fluid and fetal tissue were collected upon slaughter from the sows during the first 4 measurement periods. The empty uterus and uterine fluid contents were weighed. Individual fetuses were weighed and their length measured. Neonatal pigs from 6 sows were killed by electric shock before colostrum consumption. The fetuses and neonates were subsequently frozen, ground, and analyzed for water, protein, ash, and fat. The mineral profile was determined for the entire litter by inductively coupled plasma analysis technology. The sow and litter was each considered the experimental unit for all measurements and mineral compositions with regression analysis determined from 45 to 115 d of gestation. Results demonstrated that fetal weight increased quadratically (P < 0.01) and uterine fluid increased quadratically (P < 0.01) from 45 to 62 d, but then declined to 100 d postcoitum. The water, protein, ash, and lipid content of the fetus increased quadratically (P < 0.01) from 45 to 115 d of development, with the greatest increase of each component occurring during the last 15 d of development. Each of the macro- and microminerals increased curvilinearly (P < 0.01) as fetal development progressed with approximately 50% of the total litter and fetal macro- and micromineral contents occurring during the last 15 d of gestation. These results indicate that there is a large increase in mineral contents of fetal pigs during late gestation and that there may

  4. Radiation-induced apoptosis in developing fetal rat cerebral cortex

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Woong Ki; Nam, Taek Keun; Lee, Min Cheol; Ahn, Sung Ja; Song, Ju Young; Park, Seung Jin; Nah, Byung Sik [College of Medicine, Chonnam National Univ., Gwangju (Korea, Republic of)

    2003-09-01

    The study was performed to investigate apoptosis by radiation in the developing fetal rat brain. Fetal brains were irradiated in utero between the 17th and 19th days of fetal life(E17-19) by linear accelerator. A dose of irradiation ranging from 1 Gy to 4 Gy was used to evaluate dose dependency. To test time dependency the rats were irradiated with 2 Gy and then the fetal brain specimens were removed at variable time course; 1, 3, 6, 12 and 24 hours after the onset of irradiation. Immunohistochemical staining using in situ TdT-mediated dUTP nick end labelling (TUNEL) technique was used for apoptotic cells. The cerebral cortex, including three zones of cortical zone (CZ), intermediate zone (IZ), and ventricular zone (VZ), was examined. TUNEL positive cells revealed typical features of apoptotic cells under light microscope in the fetal rat cerebral cortex. Apoptotic cells were not found in the cerebral cortex of non-irradiated fetal rats, but did appear in the entire cerebral cortex after 1 Gy irradiation, and were more extensive at the ventricular and intermediate zones than at the cortical zone. The extent of apoptosis was increased with increasing doses of radiation. Apoptosis reached the peak at 6 hours after the onset of 2 Gy irradiation and persisted until 24 hours. Typical morphologic features of apoptosis by irradiation were observed in the developing fetal rat cerebral cortex. It was more extensive at the ventricular and intermediate zones than at the cortical zone, which suggested that stem cells or early differentiating cells are more radiosensitive than differentiated cells of the cortical zone.

  5. Fetal programming of infant neuromotor development: the generation R study.

    Science.gov (United States)

    van Batenburg-Eddes, Tamara; de Groot, Laila; Steegers, Eric A P; Hofman, Albert; Jaddoe, Vincent W V; Verhulst, Frank C; Tiemeier, Henning

    2010-02-01

    The objective of the study was to examine whether infant neuromotor development is determined by fetal size and body symmetry in the general population. This study was embedded within the Generation R Study, a population-based cohort in Rotterdam. In 2965 fetuses, growth parameters were measured in mid-pregnancy and late pregnancy. After birth, at age 9 to 15 wks, neuromotor development was assessed with an adapted version of Touwen's Neurodevelopmental Examination. Less optimal neuromotor development was defined as a score in the highest tertile. We found that higher fetal weight was beneficial to infant neurodevelopment. A fetus with a 1-SD score higher weight in mid-pregnancy had an 11% lower risk of less optimal neuromotor development (OR: 0.89; 95% CI: 0.82-0.97). Similarly, a fetus with a 1-SD score larger abdominal-to-head circumference (AC/HC) ratio had a 13% lower risk of less optimal neuromotor development (OR: 0.87; 95% CI: 0.79-0.96). These associations were also present in late pregnancy. Our findings show that fetal size and body symmetry in pregnancy are associated with infant neuromotor development. These results suggest that differences in infant neuromotor development, a marker of behavioral and cognitive problems, are at least partly caused by processes occurring early in fetal life.

  6. Changes of multiple biotransformation phase Ⅰ and phase Ⅱ enzyme activities in human fetal adrenals during fetal development

    Institute of Scientific and Technical Information of China (English)

    Hui WANG; Jie PING; Ren-xiu PENG; Jiang YUE; Xue-yan XIA; Qi-xiong LI; Rui KONG; Jun-yan HONG

    2008-01-01

    Aim: Fetal adrenal, which synthesizes steroid hormones, is critical to fetal growth and development. Our recent research showed that some xenobiotics could inter-fere with steroidogenesis and induce intrauterine growth retardation in rats. The study on the characteristics of biotransformation enzymes in fetal adrenals still seems to be important with respect to possible significance in xenobiotic-induced fetal development toxicity. In this study, the activities of several important xenobiotic-related phase Ⅰ and phase Ⅱ enzymes in human fetal adrenals were examined and compared with those in fetal livers. Methods: The activity and mRNA expression were determined by enzymatic analysis and RT-PCR. Results: The levels of cytochrome (CYP)2A6, CYP2E1, and CYP3A7 isozymes in fetal adrenals were 82%, 92%, and 33% of those in fetal livers, respectively. There was a good positive correlation between adrenal CYP2A6 activity and gestational time. The values of α glutathione S-transferase (GST), πGST, and μGST in adrenals were 0.5, 4.4, and 8.3-fold of those in the livers, respectively, and the activity of adrenal πGST was negatively correlated with gestational time. The uridine diphosphoglucuronyl transferase activities, which were measured using p-hydroxy-biphenyl and 7-hydroxy-4-methylcoumarin as substrates, were 9% and 3%, respectively, of those in the fetal livers. Conclusion: Our investiga-tion suggested that adrenal could be an important xenobiotic-metabolizing or-gan in fetal development and may play a potential role in xenobiotic-induced fetal development toxicity.

  7. Varicella zoster virus infection of human fetal lung cells alters mitochondrial morphology.

    Science.gov (United States)

    Keller, Amy C; Badani, Hussain; McClatchey, P Mason; Baird, Nicholas L; Bowlin, Jacqueline L; Bouchard, Ron; Perng, Guey-Chuen; Reusch, Jane E B; Kaufer, Benedikt B; Gilden, Don; Shahzad, Aamir; Kennedy, Peter G E; Cohrs, Randall J

    2016-10-01

    Varicella zoster virus (VZV) is a ubiquitous alphaherpesvirus that establishes latency in ganglionic neurons throughout the neuraxis after primary infection. Here, we show that VZV infection induces a time-dependent significant change in mitochondrial morphology, an important indicator of cellular health, since mitochondria are involved in essential cellular functions. VZV immediate-early protein 63 (IE63) was detected in mitochondria-rich cellular fractions extracted from infected human fetal lung fibroblasts (HFL) by Western blotting. IE63 interacted with cytochrome c oxidase in bacterial 2-hybrid analyses. Confocal microscopy of VZV-infected HFL cells at multiple times after infection revealed the presence of IE63 in the nucleus, mitochondria, and cytoplasm. Our data provide the first evidence that VZV infection induces alterations in mitochondrial morphology, including fragmentation, which may be involved in cellular damage and/or death during virus infection.

  8. Center for fetal monkey gene transfer for heart, lung, and blood diseases: an NHLBI resource for the gene therapy community.

    Science.gov (United States)

    Tarantal, Alice F; Skarlatos, Sonia I

    2012-11-01

    The goals of the National Heart, Lung, and Blood Institute (NHLBI) Center for Fetal Monkey Gene Transfer for Heart, Lung, and Blood Diseases are to conduct gene transfer studies in monkeys to evaluate safety and efficiency; and to provide NHLBI-supported investigators with expertise, resources, and services to actively pursue gene transfer approaches in monkeys in their research programs. NHLBI-supported projects span investigators throughout the United States and have addressed novel approaches to gene delivery; "proof-of-principle"; assessed whether findings in small-animal models could be demonstrated in a primate species; or were conducted to enable new grant or IND submissions. The Center for Fetal Monkey Gene Transfer for Heart, Lung, and Blood Diseases successfully aids the gene therapy community in addressing regulatory barriers, and serves as an effective vehicle for advancing the field.

  9. Prenatal Foundations: Fetal Programming of Health and Development

    Science.gov (United States)

    Davis, Elysia Poggi; Thompson, Ross A.

    2014-01-01

    The fetal programming and developmental origins of disease models suggest that experiences that occur before birth can have consequences for physical and mental health that persist across the lifespan. Development is more rapid during the prenatal period as compared to any other stage of life. This introductory article considers evidence that…

  10. Fetal Testosterone, Socio-Emotional Engagement and Language Development

    Science.gov (United States)

    Farrant, Brad M.; Mattes, Eugen; Keelan, Jeff A.; Hickey, Martha; Whitehouse, Andrew J. O.

    2013-01-01

    The present study investigated the relations among fetal testosterone, child socio-emotional engagement and language development in a sample of 467 children (235 boys) from the Western Australian Pregnancy Cohort (Raine) Study. Bioavailable testosterone concentration measured in umbilical cord blood taken at birth was found to be significantly…

  11. Effects of melamine and cyanuric acid on embryo-fetal development in rats.

    Science.gov (United States)

    Kim, Sung-Hwan; Lee, In-Chul; Baek, Hyung-Seon; No, Kyeong-Woo; Shin, Dong-Ho; Moon, Changjong; Kim, Sung-Ho; Park, Seung-Chun; Kim, Jong-Choon

    2013-10-01

    After the outbreak of acute renal failure associated with melamine-contaminated pet food, melamine and melamine-related compounds have become of great interest from a toxicologic perspective. We investigated the potential effects of melamine in combination with cyanuric acid (M + CA, 1:1) on pregnant dams and embryo-fetal development in rats. M + CA was orally administered to pregnant rats from gestational days 6 through 19 at doses of 0, 3, 10, and 30 mg/kg/day of both melamine and cyanuric acid. Maternal toxicity of rats administered 30 mg/kg/day M + CA was manifested as increased incidences of clinical signs and death; gross pathologic findings; higher blood urea nitrogen and creatinine levels; lower body weight gain and food intake; decreased thymus weight; and increased heart, lung, and kidney weights. Histopathological examinations revealed an increase in the incidence of congestion, tubular necrosis/degeneration, crystals, casts, mineralization, inflammatory cells in tubules, tubular dilation, and atrophy of glomeruli in maternal kidneys, whereas fetal kidneys did not show any histopathological changes. Developmental toxicity included a decrease in fetal (28%) and placental weights and a delay in fetal ossification (n = 7). Increased incidence of gross and histopathological changes in the maternal kidney was also found in the middle dose group (n = 12). No treatment-related maternal or developmental effects were observed in the low dose group (n = 12). Under these experimental conditions, M + CA is embryotoxic at an overt maternotoxic dose in rats and the no-observed-adverse-effect level of M + CA is considered to be 3 mg/kg/day for pregnant dams and 10 mg/kg/day for embryo-fetal development.

  12. Uteroplacental circulation and fetal vascular function and development.

    Science.gov (United States)

    Thornburg, Kent L; Louey, Samantha

    2013-09-01

    Although blood flow in the placental vasculature is governed by the same physiological forces of shear, pressure and resistance as in other organs, it is also uniquely specialized on the maternal and fetal sides. At the materno-fetal interface, the independent uteroplacental and umbilicoplacental circulations must coordinate sufficiently to supply the fetus with the nutrients and substrates it needs to grow and develop. Uterine arterial flow must increase dramatically to accommodate the growing fetus. Recent evidence delineates the hormonal and endothelial mechanisms by which maternal vessels dilate and remodel during pregnancy. The umbilical circulation is established de novo during embryonic development but blood does not flow through the placenta until late in the first trimester. The umbilical circulation operates in the interest of maintaining fetal oxygenation over the course of pregnancy, and is affected differently by mechanical and chemical regulators of vascular tone compared to other organs. The processes that match placental vascular growth and fetal tissue growth are not understood, but studies of compromised pregnancies provide clues. The subtle changes that cause the failure of the normally regulated vascular processes during pregnancy have not been thoroughly identified. Likewise, practical and effective therapeutic strategies to reverse detrimental placental perfusion patterns have yet to be investigated.

  13. Prediction of postnatal outcomes in congenital diaphragmatic hernia using MRI signal intensity of the fetal lung.

    Science.gov (United States)

    Terui, K; Omoto, A; Osada, H; Hishiki, T; Saito, T; Sato, Y; Nakata, M; Komatsu, S; Ono, S; Yoshida, H

    2011-04-01

    Prognostic prediction in prenatally diagnosed congenital diaphragmatic hernia (CDH) is needed. The aim of the study was to evaluate magnetic resonance imaging (MRI) signal intensity of the fetal lung as a predictor of prognosis in CDH. The subjects consisted of 12 fetuses with prenatally diagnosed CDH, who were treated soon after the birth in our institution. They all underwent MRI at 29 to 37 weeks of gestation. The ratio of the lung signal intensity to the spinal fluid signal intensity (L/SF) was calculated using region-of-interest analysis of T2-weighted images. The relationship between L/SF and clinical data was then examined. L/SF were significantly larger in survivors compared with deaths (0.815 vs 0.614, P<0.05). In survivors, L/SF significantly correlated with duration of tracheal intubation (rs=-0.938, P<0.01). L/SF is a unique factor to predict the survival prognosis and likely to quantify the degree of pulmonary hypoplasia in CDH.

  14. Fetal lung apparent diffusion coefficient measurement using diffusion-weighted MRI at 3 Tesla: Correlation with gestational age.

    Science.gov (United States)

    Afacan, Onur; Gholipour, Ali; Mulkern, Robert V; Barnewolt, Carol E; Estroff, Judy A; Connolly, Susan A; Parad, Richard B; Bairdain, Sigrid; Warfield, Simon K

    2016-12-01

    To evaluate the feasibility of using diffusion-weighted magnetic resonance imaging (DW-MRI) to assess the fetal lung apparent diffusion coefficient (ADC) at 3 Tesla (T). Seventy-one pregnant women (32 second trimester, 39 third trimester) were scanned with a twice-refocused Echo-planar diffusion-weighted imaging sequence with 6 different b-values in 3 orthogonal diffusion orientations at 3T. After each scan, a region-of-interest (ROI) mask was drawn to select a region in the fetal lung and an automated robust maximum likelihood estimation algorithm was used to compute the ADC parameter. The amount of motion in each scan was visually rated. When scans with unacceptable levels of motion were eliminated, the lung ADC values showed a strong association with gestational age (P < 0.01), increasing dramatically between 16 and 27 weeks and then achieving a plateau around 27 weeks. We show that to get reliable estimates of ADC values of fetal lungs, a multiple b-value acquisition, where motion is either corrected or considered, can be performed. J. Magn. Reson. Imaging 2016;44:1650-1655. © 2016 International Society for Magnetic Resonance in Medicine.

  15. CFTR and Wnt/beta-catenin signaling in lung development

    Directory of Open Access Journals (Sweden)

    Love Damon

    2008-07-01

    Full Text Available Abstract Background Cystic fibrosis transmembrane conductance regulator (CFTR was shown previously to modify stretch induced differentiation in the lung. The mechanism for CFTR modulation of lung development was examined by in utero gene transfer of either a sense or antisense construct to alter CFTR expression levels. The BAT-gal transgenic reporter mouse line, expressing β-galactosidase under a canonical Wnt/β-catenin-responsive promoter, was used to assess the relative roles of CFTR, Wnt, and parathyroid hormone-related peptide (PTHrP in lung organogenesis. Adenoviruses containing full-length CFTR, a short anti-sense CFTR gene fragment, or a reporter gene as control were used in an intra-amniotic gene therapy procedure to transiently modify CFTR expression in the fetal lung. Results A direct correlation between CFTR expression levels and PTHrP levels was found. An inverse correlation between CFTR and Wnt signaling activities was demonstrated. Conclusion These data are consistent with CFTR participating in the mechanicosensory process essential to regulate Wnt/β-Catenin signaling required for lung organogenesis.

  16. Spatiotemporal patterns of gene expression during fetal monkey brain development.

    Science.gov (United States)

    Redmond, D Eugene; Zhao, Ji-Liang; Randall, Jeffry D; Eklund, Aron C; Eusebi, Leonard O V; Roth, Robert H; Gullans, Steven R; Jensen, Roderick V

    2003-12-19

    Human DNA microarrays are used to study the spatiotemporal patterns of gene expression during the course of fetal monkey brain development. The 444 most dynamically expressed genes in four major brain areas are reported at five different fetal ages. The spatiotemporal profiles of gene expression show both regional specificity as well as waves of gene expression across the developing brain. These patterns of expression are used to identify statistically significant clusters of co-regulated genes. This study demonstrates for the first time in the primate the relevance, timing, and spatial locations of expression for many developmental genes identified in other animals and provides clues to the functions of many unknowns. Two different microarray platforms are used to provide high-throughput cross validation of the most important gene expression changes. These results may lead to new understanding of brain development and new strategies for treating and repairing disorders of brain function.

  17. DNA Methylation Landscapes of Human Fetal Development

    NARCIS (Netherlands)

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

    2015-01-01

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

  18. Regeneration of the lung: Lung stem cells and the development of lung mimicking devices.

    Science.gov (United States)

    Schilders, Kim A A; Eenjes, Evelien; van Riet, Sander; Poot, André A; Stamatialis, Dimitrios; Truckenmüller, Roman; Hiemstra, Pieter S; Rottier, Robbert J

    2016-04-23

    Inspired by the increasing burden of lung associated diseases in society and an growing demand to accommodate patients, great efforts by the scientific community produce an increasing stream of data that are focused on delineating the basic principles of lung development and growth, as well as understanding the biomechanical properties to build artificial lung devices. In addition, the continuing efforts to better define the disease origin, progression and pathology by basic scientists and clinicians contributes to insights in the basic principles of lung biology. However, the use of different model systems, experimental approaches and readout systems may generate somewhat conflicting or contradictory results. In an effort to summarize the latest developments in the lung epithelial stem cell biology, we provide an overview of the current status of the field. We first describe the different stem cells, or progenitor cells, residing in the homeostatic lung. Next, we focus on the plasticity of the different cell types upon several injury-induced activation or repair models, and highlight the regenerative capacity of lung cells. Lastly, we summarize the generation of lung mimics, such as air-liquid interface cultures, organoids and lung on a chip, that are required to test emerging hypotheses. Moreover, the increasing collaboration between distinct specializations will contribute to the eventual development of an artificial lung device capable of assisting reduced lung function and capacity in human patients.

  19. Antenatal endotoxin disrupts lung vitamin D receptor and 25-hydroxyvitamin D 1α-hydroxylase expression in the developing rat.

    Science.gov (United States)

    Mandell, Erica; Seedorf, Gregory J; Ryan, Sharon; Gien, Jason; Cramer, Scott D; Abman, Steven H

    2015-11-01

    Vitamin D [vit D; 1,25-(OH)2D] treatment improves survival and lung alveolar and vascular growth in an experimental model of bronchopulmonary dysplasia (BPD) after antenatal exposure to endotoxin (ETX). However, little is known about lung-specific 1,25-(OH)2D3 regulation during development, especially regarding maturational changes in lung-specific expression of the vitamin D receptor (VDR), 1α-hydroxylase (1α-OHase), and CYP24A1 during late gestation and the effects of antenatal ETX exposure on 1,25-(OH)2D3 metabolism in the lung. We hypothesized that vit D regulatory proteins undergo maturation regulation in the late fetal and early neonatal lung and that prenatal exposure to ETX impairs lung growth partly through abnormal endogenous vit D metabolism. Normal fetal rat lungs were harvested between embryonic day 15 and postnatal day 14. Lung homogenates were assayed for VDR, 1α-OHase, and CYP24A1 protein contents by Western blot analysis. Fetal rats were injected on embryonic day 20 with intra-amniotic ETX, ETX + 1,25-(OH)2D3, or saline and delivered 2 days later. Pulmonary artery endothelial cells (PAECs) from fetal sheep were assessed for VDR, 1α-OHase, and CYP24A1 expression after treatment with 25-(OH)D3, 1,25-(OH)2D3, ETX, ETX + 25-(OH)D3, or ETX + 1,25-(OH)2D3. We found that lung VDR, 1α-OHase, and CYP2741 protein expression dramatically increase immediately before birth (P < 0.01 vs. early fetal values). Antenatal ETX increases CYP24A1 expression (P < 0.05) and decreases VDR and 1α-OHase expression at birth (P < 0.001), but these changes are prevented with concurrent vit D treatment (P < 0.001). ETX-induced reduction of fetal PAEC growth and tube formation and lung 1α-OHase expression are prevented by vit D treatment (P < 0.001). We conclude that lung VDR, 1α-OHase, and CYP24A1 protein content markedly increase before birth and that antenatal ETX disrupts lung vit D metabolism through downregulation of VDR and increased vit D catabolic enzyme

  20. Fetal Research

    Science.gov (United States)

    Hansen, John T.; Sladek, John R.

    1989-11-01

    This article reviews some of the significant contributions of fetal research and fetal tissue research over the past 20 years. The benefits of fetal research include the development of vaccines, advances in prenatal diagnosis, detection of malformations, assessment of safe and effective medications, and the development of in utero surgical therapies. Fetal tissue research benefits vaccine development, assessment of risk factors and toxicity levels in drug production, development of cell lines, and provides a source of fetal cells for ongoing transplantation trials. Together, fetal research and fetal tissue research offer tremendous potential for the treatment of the fetus, neonate, and adult.

  1. Commercialization and Industrial Development for the Fetal Hear Rate Monitor

    Science.gov (United States)

    Zahorian, Stephen

    2000-01-01

    The primary objectives for this task were to continue the development and testing of the NASA/ODU passive acoustic fetal heart rate monitor, with the goal of transferring the technology to the commercial sector. Areas of work included: 1. To assist in the development of a new hardware front end electronics box for the fetal heart rate monitor, so as to reduce the size of the electronics box, and also to provide for a "low-frequency" and "high-frequency" mode of operation. To make necessary changes in the operating software to support the two modes of operation. 2. To provide an option for a strip chart recording for the system, so that medical personnel could more easily make comparisons with ultra sound strip chart recordings. and 3. To help with continued testing of the system.

  2. Fetal Neurobehavioral Development and the Role of Maternal Nutrient Intake and Psychological Health

    Science.gov (United States)

    Spann, Marisa; Smerling, Jennifer; Gustafsson, Hanna C.; Foss, Sophie; Monk, Catherine

    2014-01-01

    Measuring and understanding fetal neurodevelopment provides insight regarding the developing brain. Maternal nutrient intake and psychological stress during pregnancy each impact fetal neurodevelopment and influence childhood outcomes and are thus important factors to consider when studying fetal neurobehavioral development. The authors provide an…

  3. [Development of the lung cancer diagnostic system].

    Science.gov (United States)

    Lv, You-Jiang; Yu, Shou-Yi

    2009-07-01

    To develop a lung cancer diagnosis system. A retrospective analysis was conducted in 1883 patients with primary lung cancer or benign pulmonary diseases (pneumonia, tuberculosis, or pneumonia pseudotumor). SPSS11.5 software was used for data processing. For the relevant factors, a non-factor Logistic regression analysis was used followed by establishment of the regression model. Microsoft Visual Studio 2005 system development platform and VB.Net corresponding language were used to develop the lung cancer diagnosis system. The non-factor multi-factor regression model showed a goodness-of-fit (R2) of the model of 0.806, with a diagnostic accuracy for benign lung diseases of 92.8%, a diagnostic accuracy for lung cancer of 89.0%, and an overall accuracy of 90.8%. The model system for early clinical diagnosis of lung cancer has been established.

  4. [Effect of airborne particulate matter exposure on pregnancy and fetal development in female mice].

    Science.gov (United States)

    Hong, Xin-ru; Wang, Yu-mei; Liu, Chao-bin; Hu, Dian; Song, Yan-feng; Zheng, Ling; Chen, Xiao-qiu

    2011-01-01

    To investigate subacute exposure of airborne particulate matter (PM) on pregnancy and fetal development in female mice. Forty female and forty male ICR adult mice were caged separately by 1:1 to get access to pregnancy. The pregnant mice were randomized into control group (A), small (B), middle (C), large (D) or overdose (E) PM challenge groups (n = 8-11), and were administered with 30 µl of phosphate buffered solution (A) or resuspended standard PM SRM 1649a at 0.09 (B), 0.52 (C), 1.85 (D) or 69.2 (E) µg/µl, once per trid from d 0 till d 19 of pregnancy via instillation onto the base of the tongue. Fetal mice were harvested by cesarean section at the time when spontaneous delivery occurred. Body weight of the pregnant mice, gestational days, intrauterine survival and growth, hepatic and pneumonic histopathological changes of the fetal mice were investigated. Lung/body and liver/body weight ratios were calculated. Expressions of mRNA and protein of CYP1A1 in the fetal lung and CYP1A2 in the fetal liver were assayed. (1) All of the pregnant mice survived pregnancy throughout the entire experiment. Body weight of the pregnant mice was not significantly different among all the groups at gestational d 1 and 7 (P > 0.05), but significantly lower in group E [(41.8 ± 5.8) and (48.9 ± 8.9) g] than in group A [(45.9 ± 1.8) and (56.2 ± 4.9) g] at gestational d 14 and 18 (P 0.05). Lung/body and liver/body weight ratios of the fetal mice were significantly increased in group E [(1.21 ± 0.18) and (4.68 ± 0.21)%] as compared with groups A, B, C and D (P 0.05) despite of an increasing tendency. (3) Pathological changes in the liver and lung of the fetuses were conspicuous in group E. The fetal liver injury was histopathologically evidenced by deranged tissue structure, degenerated parenchyma of hepatic cells, and mildly stained cytoplasm. Adipose degeneration was represented by clear-boundary intracytoplasmic vacuoles in most of the liver cells, and cell pyknosis with

  5. Effect of vitamin E on lung development and vascular remodeling in fetal rats with congenital diaphragmatic hernia%维生素E对先天性膈疝大鼠模型胎仔肺发育及肺血管重构的影响

    Institute of Scientific and Technical Information of China (English)

    林涵; 王銮虹; 刘文英; 王学军; 吉毅; 杨纲

    2012-01-01

    Objective To discuss the effect of vitamin E on lung development and vascular remodeling in fetal rats with congenital diaphragmatic hernia (CDH). Methods Eighteen pregnant SD rats were randomly divided into 3 groups; control group, CDH group and intervention group. Rats in CDH group and intervention group underwent intragastric administration with nitrofen 125 mg ( soluble in olive oil 2 ml). Rats in control group were given olive oil 2 ml. Rats in intervention group were given vitamin E 140 mg/kg ( soluble in alcohol 2 ml) q. D for 3 days from the 11 th day of pregnancy. CDH group and intervention group were given alcohol 2 ml. Results Incidence of teratogenesis caused by diaphragmatic hernia in intervention group was less than that in CDH group (46. 34% vs 66. 67% , P<0. 05 ). Fetal rats in control group and CDH group showed similar lung development. The lung weight/body weight ratio, axial gland alveolus count ( RAC) , pulmonary alveolus area proportion and pulmonary alveolus area ratio in intervention group were significantly higher than those in CDH group [(3.45±0.58) mg/g vs (2.36±0.61) mg/g,4.4±0.3 vs2.3±0.2, (63.7±5.6)% vs ( 46. 5 ±7. 3) % , (45 ±6)% vs(27±6.7)%,P<0.01]. The alveolar septum area ratio in intervention group was significantly lower than that in CDH group [(45±6.8)% vs (63±8.3)% , P < 0.01]. The mean media thickness percentage of pre-acinar pulmonary arteries and that of intra-acinar pulmonary arteries of fetal rats in intervention group were significantly lower than those in CDH group [(22. 1±2.2)% vs (24.3±4.0)% , (17.6±2.8)% vs (21.5±2.9)% , P < 0.01 ]. The proportion of non-muscle arteries in IAPA per unit of visual field in intervention group was significantly higher than that in CDH group [(79.4±3.2)% vs (71.6±3.3)%, P< 0.01]. Conclusions Prenatal treatment with vitamin E can decrease the incidence of CDH, which may improve the lung development and inhibit the vascular remodeling in lung.%目的 探讨维生素E对先

  6. Avaliação da maturidade pulmonar fetal em gestações de alto risco Prenatal diagnosis of fetal lung maturity in high-risk pregnancies

    Directory of Open Access Journals (Sweden)

    Wladimir Taborda

    1998-07-01

    in 121 consecutive high-risk gestations at the São Paulo Hospital from January 1990 to January 1995. Delivery occurred within 3 days of fetal lung maturation testing. This is a prospective study in which the sensitivity, specificity, positive (PPV and negative predictive value (NPV of all the tests were determined. Neonatal respiratory outcome and amniocentesis results were stratified by gestational age for comparison. The distribution of the studied population according to maternal pathology was diabetes mellitus (48, hypertensive disorders (41, Rh isoimmunization (14 and miscellaneous (18. Respiratory distress (RD was present in 33 infants (27.2%, mainly in the diabetic group. There was no false negative using lung profile (all patients and foam stability tests among hypertensive pregnancies (specificity 100%, but there were about 20% to 50% false positives in the other tests. Overall, all four tests had a low PPV: 23% for foam test, 51% for L/S ratio, 63% for PG, 61% for lung profile, and high NPV: 92% for foam test, 88% for L/S ratio, 89% for PG and 100% for lung profile. All tests had less accuracy in the diabetic pregnant women. This study shows that the presence of PG and L/S ratio > 1.7 in the amniotic fluid of high-risk pregnancies confirms maturity with a very low risk to develop RD and that the foam stability test was useful as a first-line test to predict the absence of surfactant-deficient respiratory distress syndrome, particularly in hypertensive pregnant women.

  7. Infant Behavior and Development in Relation to Fetal Movement and Habituation.

    Science.gov (United States)

    Madison, Lynda S.; And Others

    1986-01-01

    Evaluated the relation between fetal activity and postnatal behavior and development by measuring the amount of fetal movement occurring in response to stimulation and the number of stimulus applications necessary for habituation. Preliminary evidence suggests that fetal rate of habituation predicts some aspects of infant behavior and development…

  8. Abnormal lung development in congenital diaphragmatic hernia.

    Science.gov (United States)

    Ameis, Dustin; Khoshgoo, Naghmeh; Keijzer, Richard

    2017-06-01

    The outcomes of patients diagnosed with congenital diaphragmatic hernia (CDH) have recently improved. However, mortality and morbidity remain high, and this is primarily caused by the abnormal lung development resulting in pulmonary hypoplasia and persistent pulmonary hypertension. The pathogenesis of CDH is poorly understood, despite the identification of certain candidate genes disrupting normal diaphragm and lung morphogenesis in animal models of CDH. Defects within the lung mesenchyme and interstitium contribute to disturbed distal lung development. Frequently, a disturbance in the development of the pleuroperitoneal folds (PPFs) leads to the incomplete formation of the diaphragm and subsequent herniation. Most candidate genes identified in animal models have so far revealed relatively few strong associations in human CDH cases. CDH is likely a highly polygenic disease, and future studies will need to reconcile how disturbances in the expression of multiple genes cause the disease. Herein, we summarize the available literature on abnormal lung development associated with CDH. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Regeneration of the lung: Lung stem cells and the development of lung mimicking devices

    NARCIS (Netherlands)

    K.A.A. Schilders (Kim); Eenjes, E. (Evelien); Riet, S. (Sander van); Poot, A.A. (André A.); Stamatialis, D. (Dimitrios); Truckenmüller, R. (Roman); P.S. Hiemstra (Pieter); R.J. Rottier (Robbert)

    2016-01-01

    textabstractInspired by the increasing burden of lung associated diseases in society and an growing demand to accommodate patients, great efforts by the scientific community produce an increasing stream of data that are focused on delineating the basic principles of lung development and growth, as

  10. Regeneration of the lung: Lung stem cells and the development of lung mimicking devices

    NARCIS (Netherlands)

    Schilders, K.; Eenjes, E.; van Riet, S.; Poot, Andreas A.; Stamatialis, Dimitrios; Truckenmüller, R.K.; Hiemstra, P.; Rottier, R.

    2016-01-01

    Inspired by the increasing burden of lung associated diseases in society and an growing demand to accommodate patients, great efforts by the scientific community produce an increasing stream of data that are focused on delineating the basic principles of lung development and growth, as well as

  11. [Diagnosis of fetal malformations with ultrasound--state of development].

    Science.gov (United States)

    Fendel, M; Fendel, H

    1983-01-01

    Ultrasonography is of great importance for the prenatal diagnosis of fetal malformations and abnormalities. An early diagnosis in the second trimester is of great interest for an intrauterine or an extrauterine therapy planning (the choice of the time and mode of delivery). Defects of the neural tube including hydrocephalus, malformations of the extremities, the gastrointestinal tract, omphaloceles, the urogenital and cardiac system are described. Four cases of fetal malformations are presented: fetal myelomeningocele, hydrocephalus, bilateral hydronephrosis and lymphangioma with fetal ascites.

  12. Soluble leukocyte-Associated Ig-like Receptor-1 in amniotic fluid is of fetal origin and positively associates with lung compliance.

    Science.gov (United States)

    Houben, Michiel L; Olde Nordkamp, Marloes J M; Nikkels, Peter G J; van der Ent, Cornelis K; Meyaard, Linde; Bont, Louis

    2013-01-01

    The soluble form of the inhibitory immune receptor leukocyte-Associated Ig-like Receptor-1 (sLAIR-1) is present in plasma, urine and synovial fluid and correlates to inflammation. We and others previously showed inflammatory protein expression in normal amniotic fluid at term. We hypothesized that sLAIR-1 is present in amniotic fluid during term parturition and is related to fetal lung function development. sLAIR-1 was detectable in all amniotic fluid samples (n=355) collected during term spontaneous deliveries. First, potential intra-uterine origins of amniotic fluid sLAIR-1 were explored. Although LAIR-1 was expressed on the surface of amniotic fluid neutrophils, LAIR-1 was not secreted upon ex vivo neutrophil stimulation with LPS, or PMA/ionomycin. Cord blood concentrations of sLAIR-1 were fourfold lower than and not related to amniotic fluid concentrations and placentas showed no or only sporadic LAIR-1 positive cells. Similarly, in post-mortem lung tissue of term neonates that died of non-pulmonary disorders LAIR-1 positive cells were absent or only sporadically present. In fetal urine samples, however, sLAIR-1 levels were even higher than in amniotic fluid and correlated with amniotic fluid sLAIR-1 concentrations. Second, the potential relevance of amniotic fluid sLAIR-1 was studied. sLAIR-1 concentrations had low correlation to amniotic fluid cytokines. We measured neonatal lung function in a convenient subset of 152 infants, using the single occlusion technique, at a median age of 34 days (IQR 30-39). The amniotic fluid concentration of sLAIR-1 was independently correlated to airway compliance (ρ=0.29, P=.001). Taken together, we show the consistent presence of sLAIR-1 in amniotic fluid, which originates from fetal urine. Concentrations of sLAIR-1 in amniotic fluid during term deliveries are independent from levels of other soluble immune mediators. The positive association between concentrations of amniotic fluid sLAIR-1 and neonatal lung compliance

  13. Soluble leukocyte-Associated Ig-like Receptor-1 in amniotic fluid is of fetal origin and positively associates with lung compliance.

    Directory of Open Access Journals (Sweden)

    Michiel L Houben

    Full Text Available The soluble form of the inhibitory immune receptor leukocyte-Associated Ig-like Receptor-1 (sLAIR-1 is present in plasma, urine and synovial fluid and correlates to inflammation. We and others previously showed inflammatory protein expression in normal amniotic fluid at term. We hypothesized that sLAIR-1 is present in amniotic fluid during term parturition and is related to fetal lung function development. sLAIR-1 was detectable in all amniotic fluid samples (n=355 collected during term spontaneous deliveries. First, potential intra-uterine origins of amniotic fluid sLAIR-1 were explored. Although LAIR-1 was expressed on the surface of amniotic fluid neutrophils, LAIR-1 was not secreted upon ex vivo neutrophil stimulation with LPS, or PMA/ionomycin. Cord blood concentrations of sLAIR-1 were fourfold lower than and not related to amniotic fluid concentrations and placentas showed no or only sporadic LAIR-1 positive cells. Similarly, in post-mortem lung tissue of term neonates that died of non-pulmonary disorders LAIR-1 positive cells were absent or only sporadically present. In fetal urine samples, however, sLAIR-1 levels were even higher than in amniotic fluid and correlated with amniotic fluid sLAIR-1 concentrations. Second, the potential relevance of amniotic fluid sLAIR-1 was studied. sLAIR-1 concentrations had low correlation to amniotic fluid cytokines. We measured neonatal lung function in a convenient subset of 152 infants, using the single occlusion technique, at a median age of 34 days (IQR 30-39. The amniotic fluid concentration of sLAIR-1 was independently correlated to airway compliance (ρ=0.29, P=.001. Taken together, we show the consistent presence of sLAIR-1 in amniotic fluid, which originates from fetal urine. Concentrations of sLAIR-1 in amniotic fluid during term deliveries are independent from levels of other soluble immune mediators. The positive association between concentrations of amniotic fluid sLAIR-1 and neonatal lung

  14. In utero development of fetal thirst and appetite: potential for programming.

    Science.gov (United States)

    El-Haddad, M A; Desai, M; Gayle, D; Ross, M G

    2004-04-01

    Thirst and appetite-mediated ingestive behavior develop and are likely programmed in utero, thus preparing for newborn and adult ingestive behavior. Fetal swallowing activity is markedly different from that of the adult, as spontaneous fetal swallowing occurs at a markedly (six-fold) higher rate compared with spontaneous adult drinking activity. This high rate of fetal swallowing is critical for the regulation of amniotic fluid volume and the development of the fetal gastrointestinal tract. Disordered fetal swallowing has been associated with both a decrease (oligohydramnios) and increase (polyhydramnios) in amniotic fluid volume. Both conditions are associated with a significant increase in perinatal morbidity and mortality, and limited treatment modalities are currently available. The mechanisms underlying the high rate of human fetal swallowing are regulated, in part, by tonic activity of central angiotensin II, glutamate N-methyl-D-aspartate receptors, and neuronal nitric oxide synthase. Fetal hypertonicity-mediated dipsogenesis is likely programmed in utero, as offspring of water-restricted ewes demonstrate a programmed syndrome of plasma hypertonicity, with significant hematologic and cardiovascular alterations. Similar to dipsogenic mechanisms, peripheral and central fetal orexic mechanisms also develop in utero, as demonstrated by increased fetal swallowing after both oral sucrose infusion and central injection of neuropeptide Y. The role of leptin in regulating fetal ingestive behavior is interesting because, contrary to actions in adults, leptin does not suppress fetal ingestive behavior. Teleologically, this may be of value during the newborn period, as unopposed appetite stimulatory mechanisms may facilitate rapid fetal and newborn weight gain. An adverse intrauterine environment, with altered fetal orexic factors during the critical developmental period of fetal life, may alter the normal setpoints of appetitive behavior and potentially lead to

  15. Exposure to Smoke During Development: Fetal Programming of Adult Disease

    Directory of Open Access Journals (Sweden)

    Bergen Hugo T

    2006-08-01

    Full Text Available Abstract It is well established that smoking has potent effects on a number of parameters including food intake, body weight, metabolism, and blood pressure. For example, it is well documented that 1 there is an inverse relationship between smoking and body weight, and 2 smoking cessation is associated with weight gain. However, there is increasing evidence that smoking can exert deleterious effects on energy balance through maternal exposure during fetal development. Specifically, there appears to be an increased incidence of metabolic disease (including obesity, and cardiovascular disease in children and adults that were exposed to smoke during fetal development. The present review will examine the relationship between maternal smoke and adult disease in offspring. The epidemiological studies highlighting this relationship will be reviewed as well as the experimental animal models that point to potential mechanisms underlying this relationship. A better understanding of how smoking effects changes in energy balance may lead to treatments to ameliorate the long-lasting effects of perinatal exposure to smoke as well as increasing the health benefits associated with smoking cessation.

  16. Gene expression during development of fetal and adult Leydig cells.

    Science.gov (United States)

    Dong, Lei; Jelinsky, Scott A; Finger, Joshua N; Johnston, Daniel S; Kopf, Gregory S; Sottas, Chantal M; Hardy, Matthew P; Ge, Ren-Shan

    2007-12-01

    In rats and mice, Leydig cells are formed as two morphologically and functionally different generations. The first generation develops in utero, from undifferentiated stem Leydig cells (SLCs) that differentiate into fetal Leydig cells (FLCs). After birth, SLCs that may differ from the fetal SLCs undergo lineage-specific commitment and give rise to adult Leydig cells (ALCs). The intermediates of ALCs first become apparent by day 11 postpartum. These first-appearing intermediates, progenitor Leydig cells (PLCs), are spindle shaped and identifiable as steroidogenic because they express luteinizing hormone receptor (LHR) and 3beta-hydroxysteroid dehydrogenase (3betaHSD). The next step in the transition of PLCs to ALCs is the appearance of the immature Leydig cells (ILCs), most commonly seen in the testis during days 28 to 56 postpartum. ILCs have a more abundant smooth endoplasm reticulum (SER), the network of membranes providing a scaffold for steroidogenic enzyme localization, compared to PLCs, but are considered immature because they secrete higher levels of 5alpha-reduced androgen than testosterone. ILCs undergo a final division before ALC steroidogenic function matures by postnatal day 56. ALCs mark the point of maximum differentiation, and at this stage, the Leydig cell secretes testosterone at the highest rate. In this review, trends of gene expression during development of the two Leydig-cell generations, and recent information from gene profiling by microarray, are evaluated. The expression profiles are distinct, indicating that FLCs and ALCs may originate from separate pools of stem cells.

  17. Embryologic and Fetal Development of the Human Eyelid

    Science.gov (United States)

    Abdulhafez, Mohamed H.; Fouad, Yousef A.; Dutton, Jonathan J.

    2016-01-01

    Purpose: To review the recent data about eyelid morphogenesis, and outline a timeline for eyelid development from the very early stages during embryonic life till final maturation of the eyelid late in fetal life. Methods: The authors extensively review major studies detailing human embryologic and fetal eyelid morphogenesis. These studies span almost a century and include some more recent cadaver studies. Numerous studies in the murine model have helped to better understand the molecular signals that govern eyelid embryogenesis. The authors summarize the current findings in molecular biology, and highlight the most significant studies in mice regarding the multiple and interacting signaling pathways involved in regulating normal eyelid morphogenesis. Results: Eyelid morphogenesis involves a succession of subtle yet strictly regulated morphogenetic episodes of tissue folding, proliferation, contraction, and even migration, which may occur simultaneously or in succession. Conclusions: Understanding the extraordinary process of building eyelid tissue in embryonic life, and deciphering its underlying signaling machinery has far reaching clinical implications beyond understanding the developmental abnormalities involving the eyelids, and may pave the way for achieving scar-reducing therapies in adult mammalian wounds, or control the spread of malignancies. PMID:27124372

  18. Pulmonary Effects of Maternal Smoking on the Fetus and Child: Effects on Lung Development, Respiratory Morbidities, and Life Long Lung Health.

    Science.gov (United States)

    McEvoy, Cindy T; Spindel, Eliot R

    2017-01-01

    Maternal smoking during pregnancy is the largest preventable cause of abnormal in-utero lung development. Despite well known risks, rates of smoking during pregnancy have only slightly decreased over the last ten years, with rates varying from 5-40% worldwide resulting in tens of millions of fetal exposures. Despite multiple approaches to smoking cessation about 50% of smokers will continue to smoke during pregnancy. Maternal genotype plays an important role in the likelihood of continued smoking during pregnancy and the degree to which maternal smoking will affect the fetus. The primary effects of maternal smoking on offspring lung function and health are decreases in forced expiratory flows, decreased passive respiratory compliance, increased hospitalization for respiratory infections, and an increased prevalence of childhood wheeze and asthma. Nicotine appears to be the responsible component of tobacco smoke that affects lung development, and some of the effects of maternal smoking on lung development can be prevented by supplemental vitamin C. Because nicotine is the key agent for affecting lung development, e-cigarette usage during pregnancy is likely to be as dangerous to fetal lung development as is maternal smoking. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. MiR-221 and miR-130a regulate lung airway and vascular development.

    Directory of Open Access Journals (Sweden)

    Sana Mujahid

    Full Text Available Epithelial-mesenchymal interactions play a crucial role in branching morphogenesis, but very little is known about how endothelial cells contribute to this process. Here, we examined how anti-angiogenic miR-221 and pro-angiogenic miR-130a affect airway and vascular development in the fetal lungs. Lung-specific effects of miR-130a and miR-221 were studied in mouse E14 whole lungs cultured for 48 hours with anti-miRs or mimics to miR-130a and miR-221. Anti-miR 221 treated lungs had more distal branch generations with increased Hoxb5 and VEGFR2 around airways. Conversely, mimic 221 treated lungs had reduced airway branching, dilated airway tips and decreased Hoxb5 and VEGFR2 in mesenchyme. Anti-miR 130a treatment led to reduced airway branching with increased Hoxa5 and decreased VEGFR2 in the mesenchyme. Conversely, mimic 130a treated lungs had numerous finely arborized branches extending into central lung regions with diffusely localized Hoxa5 and increased VEGFR2 in the mesenchyme. Vascular morphology was analyzed by GSL-B4 (endothelial cell-specific lectin immunofluorescence. Observed changes in airway morphology following miR-221 inhibition and miR-130a enhancement were mirrored by changes in vascular plexus formation around the terminal airways. Mouse fetal lung endothelial cells (MFLM-91U were used to study microvascular cell behavior. Mimic 221 treatment resulted in reduced tube formation and cell migration, where as the reverse was observed with mimic 130a treatment. From these data, we conclude that miR-221 and miR-130a have opposing effects on airway and vascular morphogenesis of the developing lung.

  20. Trisomy 21 enhances human fetal erythro-megakaryocytic development

    Science.gov (United States)

    Chou, Stella T.; Opalinska, Joanna B.; Yao, Yu; Fernandes, Myriam A.; Kalota, Anna; Brooks, John S. J.; Choi, John K.; Gewirtz, Alan M.; Danet-Desnoyers, Gwenn-ael; Nemiroff, Richard L.

    2008-01-01

    Children with Down syndrome exhibit 2 related hematopoietic diseases: transient myeloproliferative disorder (TMD) and acute megakaryoblastic leukemia (AMKL). Both exhibit clonal expansion of blasts with biphenotypic erythroid and megakaryocytic features and contain somatic GATA1 mutations. While altered GATA1 inhibits erythro-megakaryocytic development, less is known about how trisomy 21 impacts blood formation, particularly in the human fetus where TMD and AMKL originate. We used in vitro and mouse transplantation assays to study hematopoiesis in trisomy 21 fetal livers with normal GATA1 alleles. Remarkably, trisomy 21 progenitors exhibited enhanced production of erythroid and megakaryocytic cells that proliferated excessively. Our findings indicate that trisomy 21 itself is associated with cell-autonomous expansion of erythro-megakaryocytic progenitors. This may predispose to TMD and AMKL by increasing the pool of cells susceptible to malignant transformation through acquired mutations in GATA1 and other cooperating genes. PMID:18812473

  1. Cell surface carbohydrate changes during embryonic and fetal skin development

    DEFF Research Database (Denmark)

    Dabelsteen, Erik; Holbrook, K; Clausen, H

    1986-01-01

    Monoclonal antibodies to four type 2 chain carbohydrate antigens were used for immunohistochemical studies of embryonic and fetal skin. The antibodies detected N-acetyllactosamine and 3 fucosyl substitutes of this, blood group antigen H, Lex, and Ley. Periderm consistently stained for N...... expressed at the early stages of development, but may later be modified either by sialylation or fucosylation into blood group H or Lex, or by Ley substances, respectively. The orderly and well-defined changes observed during skin differentiation are in agreement with other studies, which have demonstrated...... and granular cells in the epithelium. Lex stained both basal cells and intermediate cells positively, until keratinization around week 20 EGA. Ley is never expressed on basal cells. It is weakly expressed by intermediate cells from week 14 EGA. Our study demonstrates that N-acetyllactosamine is maximally...

  2. The miR-200 family and its targets regulate type II cell differentiation in human fetal lung.

    Science.gov (United States)

    Benlhabib, Houda; Guo, Wei; Pierce, Brianne M; Mendelson, Carole R

    2015-09-11

    Type II cell differentiation and expression of the major surfactant protein, SP-A, in mid-gestation human fetal lung (HFL) are induced by cAMP and inhibited by TGF-β. cAMP induction of SP-A promoter activity is mediated by increased phosphorylation and DNA binding of thyroid transcription factor-1 (TTF-1/Nkx2.1), a master regulator of lung development. To further define mechanisms for developmental induction of surfactant synthesis in HFL, herein, we investigated the potential roles of microRNAs (miRNAs, miRs). To identify and characterize differentially regulated miRNAs in mid-gestation HFL explants during type II pneumocyte differentiation in culture, we performed miRNA microarray of RNA from epithelial cells isolated from mid-gestation HFL explants before and after culture with or without Bt2cAMP. Interestingly, the miR-200 family was significantly up-regulated during type II cell differentiation; miR-200 induction was inversely correlated with expression of known targets, transcription factors ZEB1/2 and TGF-β2. miR-200 antagonists inhibited TTF-1 and surfactant proteins and up-regulated TGF-β2 and ZEB1 expression in type II cells. Overexpression of ZEB1 in type II cells decreased DNA binding of endogenous TTF-1, blocked cAMP stimulation of surfactant proteins, and inhibited miR-200 expression, whereas cAMP markedly inhibited ZEB1/2 and TGF-β. Importantly, overexpression of ZEB1 or miR-200 antagonists in HFL type II cells also inhibited LPCAT1 and ABCA3, enzymes involved in surfactant phospholipid synthesis and trafficking, and blocked lamellar body biogenesis. Our findings suggest that the miR-200 family and ZEB1, which exist in a double-negative feedback loop regulated by TGF-β, serve important roles in the developmental regulation of type II cell differentiation and function in HFL. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Leptin promotes fetal lung maturity and upregulates SP-A expression in pulmonary alveoli type-II epithelial cells involving TTF-1 activation.

    Directory of Open Access Journals (Sweden)

    Hui Chen

    Full Text Available The placental hormone leptin has important functions in fetal and neonatal growth, and prevents depressed respiration in leptin-deficient mice. The effect of leptin on respiratory distress suffered by low birth weight and premature infants has been studied. However, it is unclear how leptin enhances lung maturity in the fetus and ameliorates neonatal respiratory distress. In the present study, we found that antenatal treatment with leptin for 2 d significantly enhanced the relative alveolus area and improved the maturity of fetal lungs in a rat model of fetal growth restriction (FGR. Mean birth weight and lung wet weight were higher in the leptin-treated group than in the PBS-treated group, indicating promotion of fetal growth. Leptin upregulated the intracellular expression and extracellular secretion of surfactant protein (SP A in type-II alveolar epithelial cells (AECs in vivo and in vitro. Dual positive effects of leptin were found on protein expression and transcriptional activity of thyroid transcription factor-1 (TTF-1, a nuclear transcription essential for branching morphogenesis of the lung and expression of SP-A in type-II AECs. Knockdown of TTF-1 by RNA interference indicated that TTF-1 may play a vital role in leptin-induced SP-A expression. These results suggest that leptin may have great therapeutic potential for the treatment of FGR, and leptin-mediated SP-A induction and lung maturity of the fetus are TTF-1 dependent.

  4. Injury to the Developing Lung: experimental and clinic al aspects

    NARCIS (Netherlands)

    I.K.M. Reiss (Irwin)

    2008-01-01

    textabstractInjury to the developing lung or disturbance of normal lung development may lead to a chronic lung disease, bronchopulmonary dysplasia (BPD), which may have long-term effects. BPD is characterized by an arrest of development of the lung and the pulmonary vascular system and occurs in aro

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

    OpenAIRE

    2014-01-01

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

  6. Passive stiffness of rat skeletal muscle undernourished during fetal development

    Directory of Open Access Journals (Sweden)

    Ana Elisa Toscano

    2010-01-01

    Full Text Available OBJECTIVES: The aim of the study was to investigate the effect of fetal undernutrition on the passive mechanical properties of skeletal muscle of weaned and young adult rats. INTRODUCTION: A poor nutrition supply during fetal development affects physiological functions of the fetus. From a mechanical point of view, skeletal muscle can be also characterized by its resistance to passive stretch. METHODS: Male Wistar rats were divided into two groups according to their mother's diet during pregnancy: a control group (mothers fed a 17% protein diet and an isocaloric low-protein group (mothers fed a 7.8% protein diet. At birth, all mothers received a standardized meal ad libitum. At the age of 25 and 90 days, the soleus muscle and extensor digitorum longus (EDL muscles were removed in order to test the passive mechanical properties. A first mechanical test consisted of an incremental stepwise extension test using fast velocity stretching (500 mm/s enabling us to measure, for each extension stepwise, the dynamic stress (σd and the steady stress (σs. A second test consisted of a slow velocity stretch in order to calculate normalized stiffness and tangent modulus from the stress-strain relationship. RESULTS: The results for the mechanical properties showed an important increase in passive stiffness in both the soleus and EDL muscles in weaned rat. In contrast, no modification was observed in young adult rats. CONCLUSIONS: The increase in passive stiffness in skeletal muscle of weaned rat submitted to intrauterine undernutrition it is most likely due to changes in muscle passive stiffness.

  7. Fluorescence polarization of amniotic fluid to assess fetal lung maturity in high risk pregnancies

    Directory of Open Access Journals (Sweden)

    Tadeu Gantus Simão Stefano

    2006-06-01

    Full Text Available Objective: To assess the accuracy, sensitivity, specificity, and thepositive and negative predictive values of amniotic fluidfluorescence polarization for neonatal respiratory distresssyndrome in high risk pregnancies. Methods: A prospectivedescriptive study of 54 patients with high risk pregnancies. Fetallung maturity was assessed using amniotic fluid florescencepolarization obtained by amniocentesis up to 72 hours beforedelivery. Respiratory distress syndrome, stratified by gestationalage at birth, was the primary outcome analyzed. Amniotic fluidfluorescence polarization values equal to or over 50 mg/g (indicatingfetal lung maturity were considered as negative results. Results:The mean gestational age at birth was 35 weeks (SD 2.0.Respiratory distress syndrome was seen in 14 newborns(24%. Amniotic fluid fluorescence polarization had high sensitivity(86% and specificity (81%, with 14% false-negative and 19% falsepositiveresults. The positive predictive value was 60% and thenegative predictive value was 94%. The area under the ROC curveindicated the 50 mg/g albumin/surfactant ratio as the best cutoffpoint (85% sensitivity and 81% specificity. Conclusion: A negativevalue in amniotic fluid fluorescence polarization (results equal toor over 50 mg/g confirms lung maturity which translates into avery low risk of a newborn developing respiratory distresssyndrome in high risk pregnancies.

  8. Isolation, in vitro culture and identification of a new type of mesenchymal stem cell derived from fetal bovine lung tissues.

    Science.gov (United States)

    Hu, Pengfei; Pu, Yabin; Li, Xiayun; Zhu, Zhiqiang; Zhao, Yuhua; Guan, Weijun; Ma, Yuehui

    2015-09-01

    Lung‑derived mesenchymal stem cells (LMSCs) are considered to be important in lung tissue repair and regenerative processes. However, the biological characteristics and differentiation potential of LMSCs remain to be elucidated. In the present study, fetal lung‑derived mesenchymal stem cells (FLMSCs) were isolated from fetal bovine lung tissues by collagenase digestion. The in vitro culture conditions were optimized and stabilized and the self‑renewal ability and differentiation potential were evaluated. The results demonstrated that the FLMSCs were morphologically consistent with fibroblasts, were able to be cultured and passaged for at least 33 passages and the cell morphology and proliferative ability were stable during the first 10 passages. In addition, FLMSCs were found to express CD29, CD44, CD73 and CD166, however, they did not express hematopoietic cell specific markers, including CD34, CD45 and BOLA‑DRα. The growth kinetics of FLMSCs consisted of a lag phase, a logarithmic phase and a plateau phase, and as the passages increased, the proliferative ability of cells gradually decreased. The majority of FLMSCs were in G0/G1 phase. Following osteogenic induction, FLMSCs were positive for the expression of osteopontin and collagen type I α2. Following neurogenic differentiation, the cells were morphologically consistent with neuronal cells and positive for microtubule‑associated protein 2 and nestin expression. It was concluded that the isolated FLMSCs exhibited typical characteristics of mesenchymal stem cells and that the culture conditions were suitable for their proliferation and the maintenance of stemness. The present study illustrated the potential application of lung tissue as an adult stem cell source for regenerative therapies.

  9. Early- versus Late-Onset Fetal Growth Restriction Differentially Affects the Development of the Fetal Sheep Brain.

    Science.gov (United States)

    Alves de Alencar Rocha, Anna Karynna; Allison, Beth J; Yawno, Tamara; Polglase, Graeme R; Sutherland, Amy E; Malhotra, Atul; Jenkin, Graham; Castillo-Melendez, Margie; Miller, Suzanne L

    2017-01-01

    Fetal growth restriction (FGR) is a common complication of pregnancy, principally caused by suboptimal placental function, and is associated with high rates of perinatal mortality and morbidity. Clinical studies suggest that the time of onset of placental insufficiency is an important contributor towards the neurodevelopmental impairments that are evident in children who had FGR. It is however currently unknown how early-onset and late-onset FGR differentially affect brain development. The aim of this study was to examine neuropathology in early-onset and late-onset FGR fetal sheep and to determine whether they differentially alter brain development. We induced placental insufficiency and FGR via single umbilical artery ligation at either 88 days (early-onset) or 105 days (late-onset) of fetal sheep gestation (term is approx. 147 days), reflecting a period of rapid white matter brain development. Fetal blood samples were collected for the first 10 days after surgery, and all fetuses were sacrificed at 125 days' gestation for brain collection and subsequent histopathology. Our results show that early-onset FGR fetuses became progressively hypoxic over the first 10 days after onset of placental insufficiency, whereas late-onset FGR fetuses were significantly hypoxic compared to controls from day 1 after onset of placental insufficiency (SaO2 46.7 ± 7.4 vs. 65.7 ± 3.9%, respectively, p = 0.03). Compared to control brains, early-onset FGR brains showed widespread white matter injury, with a reduction in both CNPase-positive and MBP-positive density of staining in the periventricular white matter (PVWM), subcortical white matter, intragyral white matter (IGWM), subventricular zone (SVZ), and external capsule (p development that principally mediates altered brain development associated with FGR. © 2017 S. Karger AG, Basel.

  10. Doppler de las arterias pulmonares fetales posterior al uso de betametasona para la maduración pulmonar (Fetal lung arteries Doppler after to use of betamethasone for lung maturation

    Directory of Open Access Journals (Sweden)

    Keibis Jiménez Castillejo

    2014-06-01

    Full Text Available Resumen (español El objetivo de la investigación fue determinar las modificaciones del Doppler de las arterias pulmonares fetales posterior al uso de betametasona para la maduración pulmonar. Se realizó una investigación de tipo explicativa, prospectiva y longitudinal con un diseño cuasi-experimental y una muestra no probabilística intencional de 106 pacientes que acudieron a la consulta Pre-natal de Alto Riesgo del Hospital Central “Dr. Urquinaona". Una vez seleccionadas las pacientes se les administró inyecciones intramusculares de betametasona (12 mg/día por dos días consecutivos. Se realizaron las mediciones de índice de pulsatilidad, índice de resistencia y relación sistólico / diastólica de las arterias pulmonares fetales. Se observó disminución significativa de los valores promedio del índice de pulsatilidad en la segunda medición comparado con la medición inicial (p < 0,05. Sin embargo, el promedio de la tercera medición no mostró diferencia significativas con los valores iniciales (p = ns. El índice de resistencia disminuyó en la segunda medición para luego aumentar en la tercera medición comparado con el valor inicial (p < 0,05 para las dos mediciones. El valor promedio de la relación sistólico / diastólica presentó disminución significativa durante la segunda medición para luego presentar un aumento significativo al momento de la tercera medición comparado con el valor inicial (p < 0,05 para las dos mediciones. Se concluye que el uso de betametasona para la inducción de la maduración pulmonar produce modificaciones en las mediciones Doppler de las arterias pulmonares fetales. Abstract (english The objective of research was to determine Doppler modifications of fetal pulmonary arteries after use of betamethasone for lung maturation. An explicative, prospective and longitudinal research was done with a quasi-experimental design and an intentional non-probabilistic sample of 106 patients who assisted

  11. Development and significance of a fetal electrocardiogram recorded by signal-averaged high-amplification electrocardiography.

    Science.gov (United States)

    Hayashi, Risa; Nakai, Kenji; Fukushima, Akimune; Itoh, Manabu; Sugiyama, Toru

    2009-03-01

    Although ultrasonic diagnostic imaging and fetal heart monitors have undergone great technological improvements, the development and use of fetal electrocardiograms to evaluate fetal arrhythmias and autonomic nervous activity have not been fully established. We verified the clinical significance of the novel signal-averaged vector-projected high amplification ECG (SAVP-ECG) method in fetuses from 48 gravidas at 32-41 weeks of gestation and in 34 neonates. SAVP-ECGs from fetuses and newborns were recorded using a modified XYZ-leads system. Once noise and maternal QRS waves were removed, the P, QRS, and T wave intervals were measured from the signal-averaged fetal ECGs. We also compared fetal and neonatal heart rates (HRs), coefficients of variation of heart rate variability (CV) as a parasympathetic nervous activity, and the ratio of low to high frequency (LF/HF ratio) as a sympathetic nervous activity. The rate of detection of a fetal ECG by SAVP-ECG was 72.9%, and the fetal and neonatal QRS and QTc intervals were not significantly different. The neonatal CVs and LF/HF ratios were significantly increased compared with those in the fetus. In conclusion, we have developed a fetal ECG recording method using the SAVP-ECG system, which we used to evaluate autonomic nervous system development.

  12. Poisonous plants: effects on embryo and fetal development.

    Science.gov (United States)

    Panter, Kip E; Welch, Kevin D; Gardner, Dale R; Green, Benedict T

    2013-12-01

    Poisonous plant research in the United States began over 100 years ago as a result of livestock losses from toxic plants as settlers migrated westward with their flocks, herds, and families. Major losses were soon associated with poisonous plants, such as locoweeds, selenium accumulating plants, poison-hemlock, larkspurs, Veratrum, lupines, death camas, water hemlock, and others. Identification of plants associated with poisoning, chemistry of the plants, physiological effects, pathology, diagnosis, and prognosis, why animals eat the plants, and grazing management to mitigate losses became the overarching mission of the current Poisonous Plant Research Laboratory. Additionally, spin-off benefits resulting from the animal research have provided novel compounds, new techniques, and animal models to study human health conditions (biomedical research). The Poisonous Plant Research Laboratory has become an international leader of poisonous plant research as evidenced by the recent completion of the ninth International Symposium on Poisonous Plant Research held July 2013 in Hohhot, Inner Mongolia, China. In this article, we review plants that negatively impact embryo/fetal and neonatal growth and development, with emphasis on those plants that cause birth defects. Although this article focuses on the general aspects of selected groups of plants and their effects on the developing offspring, a companion paper in this volume reviews current understanding of the physiological, biochemical, and molecular mechanisms of toxicoses and teratogenesis.

  13. Effects of early- and late-gestational maternal stress and synthetic glucocorticoid on development of the fetal hypothalamus-pituitary-adrenal axis in sheep.

    Science.gov (United States)

    Rakers, Florian; Frauendorf, Vilmar; Rupprecht, Sven; Schiffner, Rene; Bischoff, Sabine J; Kiehntopf, Michael; Reinhold, Petra; Witte, Otto W; Schubert, Harald; Schwab, Matthias

    2013-01-01

    Prenatal maternal stress (PMS) programs dysregulation of the hypothalamus-pituitary-adrenal axis (HPAA) in postnatal life, though time periods vulnerable to PMS, are still unclear. We evaluated in pregnant sheep the effect of PMS during early gestation [30-100 days of gestation (dGA); term is 150 dGA] or late gestation (100-120 dGA) on development of fetal HPAA function. We compared the effects of endogenous cortisol with synthetic glucocorticoid (GC) exposure, as used clinically to enhance fetal lung maturation. Pregnant sheep were exposed to repeated isolation stress twice per week for 3 h in a separate box with no visual, tactile, or auditory contact with their flock-mates either during early (n = 7) or late (n = 7) gestation. Additional groups received two courses of betamethasone (BM; n = 7; 2 × 110 μg kg(- 1) body weight, 24 h apart) during late gestation (106/107 and 112/113 dGA, n = 7) or acted as controls (n = 7). Fetal cortisol responses to hypotensive challenge, a physiological fetal stressor, were measured at 112 and 129 dGA, i.e. before and during maturation of the HPAA. Hypotension was induced by fetal infusion of sodium nitroprusside, a potent vasodilator. At 112 dGA, neither PMS nor BM altered fetal cortisol responses. PMS, during early or late gestation, and BM treatment increased fetal cortisol responses at 129 dGA with the greatest increase achieved in stressed early pregnant sheep. Thus, development of the HPAA is vulnerable to inappropriate levels of GCs during long periods of fetal life, whereas early gestation is most vulnerable to PMS.

  14. Effects of maternal subtotal nephrectomy on the development of the fetal kidney: A morphometric study.

    Science.gov (United States)

    Kondo, Tomohiro; Kitano-Amahori, Yoko; Nagai, Hiroaki; Mino, Masaki; Takeshita, Ai; Kusakabe, Ken Takeshi; Okada, Toshiya

    2015-11-01

    The present study was designed to explore if maternal subtotal (5/6) nephrectomy affects the development of fetal rat kidneys using morphometric methods and examining whether there are any apoptotic changes in the fetal kidney. To generate 5/6 nephrectomized model rats, animals underwent 2/3 left nephrectomy on gestation day (GD) 5 and total right nephrectomy on GD 12. The fetal kidneys were examined on GDs 16 and 22. A significant decrease in fetal body weight resulting from maternal 5/6 nephrectomy was observed on GD 16, and a significant decrease in fetal renal weight and fetal body weight caused by maternal nephrectomy was observed on GD 22. Maternal 5/6 nephrectomy induced a significant increase in glomerular number, proximal tubular length, and total proximal tubular volume of fetuses on GD 22. Maternal 5/6 nephrectomy resulted in an increase in the number of apoptotic cells in the metanephric mesenchyme of the kidney on GD 16, and in the collecting tubules on GD 22. These findings suggest that maternal 5/6 nephrectomy stimulates the development of the fetal kidney while suppressing fetal growth.

  15. Glucocorticoids Distinctively Modulate the CFTR Channel with Possible Implications in Lung Development and Transition into Extrauterine Life.

    Directory of Open Access Journals (Sweden)

    Mandy Laube

    Full Text Available During fetal development, the lung is filled with fluid that is secreted by an active Cl- transport promoting lung growth. The basolateral Na+,K+,2Cl- cotransporter (NKCC1 participates in Cl- secretion. The apical Cl- channels responsible for secretion are unknown but studies suggest an involvement of the cystic fibrosis transmembrane conductance regulator (CFTR. CFTR is developmentally regulated with a high expression in early fetal development and a decline in late gestation. Perinatal lung transition is triggered by hormones that stimulate alveolar Na+ channels resulting in fluid absorption. Little is known on how hormones affect pulmonary Cl- channels. Since the rise of fetal cortisol levels correlates with the decrease in fetal CFTR expression, a causal relation may be assumed. The aim of this study was to analyze the influence of glucocorticoids on pulmonary Cl- channels. Alveolar cells from fetal and adult rats, A549 cells, bronchial Calu-3 and 16HBE14o- cells, and primary rat airway cells were studied with real-time quantitative PCR and Ussing chambers. In fetal and adult alveolar cells, glucocorticoids strongly reduced Cftr expression and channel activity, which was prevented by mifepristone. In bronchial and primary airway cells CFTR mRNA expression was also reduced, whereas channel activity was increased which was prevented by LY-294002 in Calu-3 cells. Therefore, glucocorticoids strongly reduce CFTR expression while their effect on CFTR activity depends on the physiological function of the cells. Another apical Cl- channel, anoctamin 1 showed a glucocorticoid-induced reduction of mRNA expression in alveolar cells and an increase in bronchial cells. Furthermore, voltage-gated chloride channel 5 and anoctamine 6 mRNA expression were increased in alveolar cells. NKCC1 expression was reduced by glucocorticoids in alveolar and bronchial cells alike. The results demonstrate that glucocorticoids differentially modulate pulmonary Cl

  16. Glucocorticoids Distinctively Modulate the CFTR Channel with Possible Implications in Lung Development and Transition into Extrauterine Life.

    Science.gov (United States)

    Laube, Mandy; Bossmann, Miriam; Thome, Ulrich H

    2015-01-01

    During fetal development, the lung is filled with fluid that is secreted by an active Cl- transport promoting lung growth. The basolateral Na+,K+,2Cl- cotransporter (NKCC1) participates in Cl- secretion. The apical Cl- channels responsible for secretion are unknown but studies suggest an involvement of the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is developmentally regulated with a high expression in early fetal development and a decline in late gestation. Perinatal lung transition is triggered by hormones that stimulate alveolar Na+ channels resulting in fluid absorption. Little is known on how hormones affect pulmonary Cl- channels. Since the rise of fetal cortisol levels correlates with the decrease in fetal CFTR expression, a causal relation may be assumed. The aim of this study was to analyze the influence of glucocorticoids on pulmonary Cl- channels. Alveolar cells from fetal and adult rats, A549 cells, bronchial Calu-3 and 16HBE14o- cells, and primary rat airway cells were studied with real-time quantitative PCR and Ussing chambers. In fetal and adult alveolar cells, glucocorticoids strongly reduced Cftr expression and channel activity, which was prevented by mifepristone. In bronchial and primary airway cells CFTR mRNA expression was also reduced, whereas channel activity was increased which was prevented by LY-294002 in Calu-3 cells. Therefore, glucocorticoids strongly reduce CFTR expression while their effect on CFTR activity depends on the physiological function of the cells. Another apical Cl- channel, anoctamin 1 showed a glucocorticoid-induced reduction of mRNA expression in alveolar cells and an increase in bronchial cells. Furthermore, voltage-gated chloride channel 5 and anoctamine 6 mRNA expression were increased in alveolar cells. NKCC1 expression was reduced by glucocorticoids in alveolar and bronchial cells alike. The results demonstrate that glucocorticoids differentially modulate pulmonary Cl- channels and are likely

  17. TET1 contributes to neurogenesis onset time during fetal brain development in mice.

    Science.gov (United States)

    Kim, Hyerim; Jang, Woo Young; Kang, Min-Cheol; Jeong, Jain; Choi, Minjee; Sung, Yonghun; Park, Song; Kwon, Wookbong; Jang, Soyoung; Kim, Myoung Ok; Kim, Sung Hyun; Ryoo, Zae Young

    2016-03-18

    Epigenetic mechanisms are relevant to development and contribute to fetal neurogenesis. DNA methylation and demethylation contribute to neural gene expression during mouse brain development. Ten-eleven translocation 1 (TET1) regulates DNA demethylation by converting 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). TET1 specifically regulates 5hmC in the central nervous system (CNS), including during neurogenesis in the adult brain. However little is known about its function in fetal neurogenesis. In order to evaluate the role of TET1 in fetal brain development, we generated TET1-overexpressing transgenic (TG) mice. TET1 overexpression was confirmed in the brains of fetal mice, and we detected 5hmC overexpression in the TG brains compared to that in the wild type (WT) brains, using a dot-blot assay. In order to observe the role of TET1 in fetal brain development, we examined fetal brain samples at varied time points by using real-time PCR, Western blotting, and Immunofluorescence (IF). We confirmed that TET1 contributes to neurogenesis by upregulating the protein expressions of neuronal markers in the TG mouse brains, as determined by Western blotting. However the cortex structure or brain mass between WT and TG mice showed no significant difference by IF. In conclusion, TET1 makes the start time of neurogenesis earlier in the TG brains compared to that in the WT brains during fetal brain development.

  18. Acquisition of innate-like microbial reactivity in mucosal tissues during human fetal MAIT-cell development

    Science.gov (United States)

    Leeansyah, Edwin; Loh, Liyen; Nixon, Douglas F.; Sandberg, Johan K.

    2014-01-01

    Innate-like, evolutionarily conserved MR1-restricted mucosa-associated invariant T (MAIT) cells represent a large antimicrobial T-cell subset in humans. Here, we investigate the development of these cells in second trimester human fetal tissues. MAIT cells are rare and immature in the fetal thymus, spleen and mesenteric lymph nodes. In contrast, mature IL-18Rα+ CD8αα MAIT cells are enriched in the fetal small intestine, liver and lung. Independently of localization, MAIT cells express CD127 and Ki67 in vivo and readily proliferate in response to Escherichia coli in vitro. Maturation is accompanied by the gradual post-thymic acquisition of the PLZF transcription factor and the ability to produce IFNγ and IL-22 in response to bacteria in mucosa. Thus, MAIT cells acquire innate-like antimicrobial responsiveness in mucosa before exposure to environmental microbes and the commensal microflora. Establishment of this arm of immunity before birth may help protect the newborn from a range of pathogenic microbes.

  19. Prenatal and postnatal genetic influence on lung function development

    DEFF Research Database (Denmark)

    Kreiner-Møller, Eskil; Bisgaard, Hans; Bønnelykke, Klaus

    2014-01-01

    BACKGROUND: It is unknown to what extent adult lung function genes affect lung function development from birth to childhood. OBJECTIVE: Our aim was to study the association of candidate genetic variants with neonatal lung function and lung function development until age 7 years. METHODS: Lung...... of methacholine causing a 20% decrease in lung function [PD20]) and with development from birth to age 7 years (FEV0.5/1, FEF50, and PD15/20). RESULTS: The genetic risk scores were not associated with lung function measures at age 1 month, but the FEV1/FVC genetic risk score was associated with reduced FEF50...... function genetic variants identified in adults were not associated with neonatal lung function or bronchial responsiveness but with the development of these lung function measures during early childhood, suggesting a window of opportunity for interventions targeting these genetic mechanisms....

  20. GROWTH RATE OF HUMAN FETAL LUNG WITH INCREASE IN GESTATIO NAL AGE: A MORPHOLOGICAL STUDY

    Directory of Open Access Journals (Sweden)

    Rajkumari

    2015-04-01

    Full Text Available AIM: The present study was designed to find out a relationship between growth rate of lung of the human fetuses at different gestational weeks and that of lung weight/body weight ratio with increase in gestational weeks. SETTINGS AND DESIGN: This morphological study was carried out at the Department of Obstetrics and Gynaecology of Regional Institute of Medical Sciences Hospital, Imphal, Manipur with the permission of the Medical Superintendent. MATERIALS AND METHODS: The study was carried ou t on 63 ( S ixty three fetuses of different gestational ages ranging from 11 th to 36 th gestational weeks obtained from the Department of Obstetrics and Gynaecology of Regional Institute of Medical Sciences Hospital, Imphal. The gross morphological parameter s such as weights of fetuses and lungs were noted. The mean  SD values of the fetuses and lung weights were measured. The data were statistically and graphically analyzed. RESULTS: The growth rate of left and right lungs showed a minimal value of about 1. 80 gm upto 13 th gestational week and thereafter showed a gradual increase from 13 th to 20 th week and then showed a moderately steep rise and was found to be almost similar upto 24 th week showing an average weight of about 18 gm. From 24 th week, the growth rate of right lung was found slightly faster than that of left lung upto the 36 th gestational week. The differential rate of the lung weight/body weight ratios was observed as follows: a steep fall from 11 th to 12 th week, then a gradual increase from 12 th to 14 th week, then a moderately steep fall from 14 th to 16 th week and then a gradual fall upto 20 th week, a gradual increase from 20 th to 24 th week, then a gradual fall from 24 th to 31 st week and then remained almost constant upto 36 th week. CONCLUSION: T he present study revealed that the growth rate of both the lungs increased gradually upto 20 th week and then a moderate steep rise from 20 th to 24 th week. A significant and

  1. Epidermal growth factor and lung development in the offspring of the diabetic rat

    DEFF Research Database (Denmark)

    Thulesen, J; Poulsen, Steen Seier; Nexø, Ebba

    2000-01-01

    Fetuses of diabetic mothers who were exposed to excessive glucose show delayed maturation. Under these conditions, altered growth factor expression or signaling may have important regulatory influences. We examined the role of epidermal growth factor (EGF) in lung development and maternal diabetes...... in the rat. In order to evaluate the possible role of glucose for the expression of EGF and the growth of lung tissue, we performed in vitro studies with organotypic cultures of fetal alveolar cells obtained from control rats. Compared to pups of normal rats, the newborn rats of untreated diabetic rats had...... and was associated with a reduced intensity of surfactant protein A-IR. The only difference observed between pups of treated diabetic rats and controls was a decrease in the lung weight:body weight ratio. In organotypic cultures, the presence of 13 mmol/L glucose in the cell media increased immunoreactive staining...

  2. Evaluation of maternal infusion therapy during pregnancy for fetal development

    Directory of Open Access Journals (Sweden)

    2005-10-01

    Full Text Available The aim of this project was to study the possible association between maternal infusion treatments during pregnancy and variables of fetal development as well as the occurrence of congenital abnormalities (CA in a case-control design. The large population-based data set of the Hungarian Case‑Control Surveillance of Congenital Abnormalities (HCCSCA was evaluated based on the medically recorded infusion treatment during pregnancy. Of 22,843 case pregnant women who had newborns or fetuses with congenital abnormalities, 112 (0.5%, while of 38,151 control pregnant women who had newborn infants without any defects, 262 (0.7%, had infusion treatment during pregnancy. Infusion treatment was more frequent in the control group than in the case group with congenital abnormalities (adjusted POR with 945 95% CI: 0.7, 0.6-0.9 and there was no higher rate of maternal infusion treatments in any congenital abnormality group. Mean gestational age was shorter and mean birth weight was smaller in control newborn infants without CA born to mothers with infusion treatment during pregnancy than in the babies of mothers without infusion treatment. The prevalence of mild intrauterine growth retardation was more frequent in the fetuses of pregnant women with hyperemesis gravidarum treated with infusion. The results of the study suggest that infusion treatment of pregnant women did not associate with a higher risk of congenital abnormalities. In addition, the intravenous infusion of drugs has some, but limited efficacy to prevent the adverse effects of hyperemesis gravidarum and threatened preterm delivery.

  3. Development of a highly balanced gradiometer for fetal magnetocardiography

    NARCIS (Netherlands)

    Uzunbajakau, S.A.

    2008-01-01

    Activation of the cardiac muscle is associated with ion transport through the membrane of the cardiac cell. This gives rise to the strongest electrophysiological signals in human body: the cardiograms. Segments of the cardiogram are related to the contraction of the hearts chambers. In fetal magneto

  4. Arginine nutrition and fetal brown adipose tissue development in nutrient-restricted sheep.

    Science.gov (United States)

    Satterfield, M Carey; Dunlap, Kathrin A; Keisler, Duane H; Bazer, Fuller W; Wu, Guoyao

    2013-09-01

    Intrauterine growth restriction is a significant problem worldwide, resulting in increased rates of neonatal morbidity and mortality, as well as increased risks for metabolic and cardiovascular disease. The present study investigated the role of maternal undernutrition and L-arginine administration on fetal growth and development. Embryo transfer was utilized to generate genetically similar singleton pregnancies. On Day 35 of gestation, ewes were assigned to receive either 50 or 100% of their nutritional requirements. Ewes received i.v. injections of either saline or L-arginine three times daily from Day 100 to Day 125. Fetal growth was assessed at necropsy on Day 125. Maternal dietary manipulation altered circulating concentrations of leptin, progesterone, and amino acids in maternal plasma. Fetal weight was reduced in nutrient-restricted ewes on Day 125 compared with 100% fed ewes. Compared with saline-treated underfed ewes, maternal L-arginine administration did not affect fetal weight but increased weight of the fetal pancreas by 32% and fetal peri-renal brown adipose tissue mass by 48%. These results indicate that L-arginine administration enhanced fetal pancreatic and brown adipose tissue development. The postnatal effects of increased pancreatic and brown adipose tissue growth warrant further study.

  5. The fetal circulation.

    Science.gov (United States)

    Kiserud, Torvid; Acharya, Ganesh

    2004-12-30

    Accumulating data on the human fetal circulation shows the similarity to the experimental animal physiology, but with important differences. The human fetus seems to circulate less blood through the placenta, shunt less through the ductus venosus and foramen ovale, but direct more blood through the lungs than the fetal sheep. However, there are substantial individual variations and the pattern changes with gestational age. The normalised umbilical blood flow decreases with gestational age, and, at 28 to 32 weeks, a new level of development seems to be reached. At this stage, the shunting through the ductus venosus and the foramen ovale reaches a minimum, and the flow through the lungs a maximum. The ductus venosus and foramen ovale are functionally closely related and represent an important distributional unit for the venous return. The left portal branch represents a venous watershed, and, similarly, the isthmus aorta an arterial watershed. Thus, the fetal central circulation is a very flexible and adaptive circulatory system. The responses to increased afterload, hypoxaemia and acidaemia in the human fetus are equivalent to those found in animal studies: increased ductus venosus and foramen ovale shunting, increased impedance in the lungs, reduced impedance in the brain, increasingly reversed flow in the aortic isthmus and a more prominent coronary blood flow.

  6. Fetal development of subcutaneous white adipose tissue is dependent on Zfp423

    Directory of Open Access Journals (Sweden)

    Mengle Shao

    2017-01-01

    Conclusions: Our results reveal that Zfp423 is essential for the terminal differentiation of subcutaneous white adipocytes during fetal adipose tissue development. Moreover, our data highlight the striking adverse effects of pathological subcutaneous adipose tissue remodeling on visceral adipose function and systemic nutrient homeostasis in obesity. Importantly, these data reveal the distinct phenotypes that can occur when adiponectin driven transgenes are activated in fetal vs. adult adipose tissue.

  7. THE FETAL ORIGINS OF MEMORY: THE ROLE OF DIETARY CHOLINE IN OPTIMAL BRAIN DEVELOPMENT

    OpenAIRE

    Steven H Zeisel

    2006-01-01

    Fetal nutrition sets the stage for organ function in later life. In this review we discuss the fetal and neonatal origins of brain function. Numerous research observations point to the importance of choline for the developing fetus and neonate. This essential nutrient is involved in 1-carbon metabolism and is the precursor for many important compounds, including phospholipids, acetylcholine, and the methyl donor betaine. Dietary intake of choline by the pregnant mother and later by the infant...

  8. Ibuprofen results in alterations of human fetal testis development

    Science.gov (United States)

    Ben Maamar, Millissia; Lesné, Laurianne; Hennig, Kristin; Desdoits-Lethimonier, Christèle; Kilcoyne, Karen R.; Coiffec, Isabelle; Rolland, Antoine D.; Chevrier, Cécile; Kristensen, David M.; Lavoué, Vincent; Antignac, Jean-Philippe; Le Bizec, Bruno; Dejucq-Rainsford, Nathalie; Mitchell, Rod T.; Mazaud-Guittot, Séverine; Jégou, Bernard

    2017-01-01

    Among pregnant women ibuprofen is one of the most frequently used pharmaceutical compounds with up to 28% reporting use. Regardless of this, it remains unknown whether ibuprofen could act as an endocrine disruptor as reported for fellow analgesics paracetamol and aspirin. To investigate this, we exposed human fetal testes (7–17 gestational weeks (GW)) to ibuprofen using ex vivo culture and xenograft systems. Ibuprofen suppressed testosterone and Leydig cell hormone INSL3 during culture of 8–9 GW fetal testes with concomitant reduction in expression of the steroidogenic enzymes CYP11A1, CYP17A1 and HSD17B3, and of INSL3. Testosterone was not suppressed in testes from fetuses younger than 8 GW, older than 10–12 GW, or in second trimester xenografted testes (14–17 GW). Ex vivo, ibuprofen also affected Sertoli cell by suppressing AMH production and mRNA expression of AMH, SOX9, DHH, and COL2A1. While PGE2 production was suppressed by ibuprofen, PGD2 production was not. Germ cell transcripts POU5F1, TFAP2C, LIN28A, ALPP and KIT were also reduced by ibuprofen. We conclude that, at concentrations relevant to human exposure and within a particular narrow ‘early window’ of sensitivity within first trimester, ibuprofen causes direct endocrine disturbances in the human fetal testis and alteration of the germ cell biology. PMID:28281692

  9. VEGF receptor expression decreases during lung development in congenital diaphragmatic hernia induced by nitrofen

    Energy Technology Data Exchange (ETDEWEB)

    Sbragia, L. [Divisão de Cirurgia Pediátrica, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil, Divisão de Cirurgia Pediátrica, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Nassr, A.C.C. [Departamento de Hidrobiologia do Centro de Ciências Biológicas e da Saúde, Universidade Federal de São Carlos, São Carlos, SP, Brasil, Departamento de Hidrobiologia do Centro de Ciências Biológicas e da Saúde, Universidade Federal de São Carlos, São Carlos, SP (Brazil); Gonçalves, F.L.L. [Divisão de Cirurgia Pediátrica, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil, Divisão de Cirurgia Pediátrica, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Schmidt, A.F. [Pediatrics House Office, Cincinnati Children' s Hospital Medical Center, Cincinnati, OH, USA, Pediatrics House Office, Cincinnati Children' s Hospital Medical Center, Cincinnati, OH (United States); Zuliani, C.C. [Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil, Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP (Brazil); Garcia, P.V. [Departamento de Histologia e Embriologia, Instituto de Biologia, Universidade Estadual de Campinas, UNICAMP, Campinas, SP, Brasil, Departamento de Histologia e Embriologia, Instituto de Biologia, Universidade Estadual de Campinas, UNICAMP, Campinas, SP (Brazil); Gallindo, R.M. [Divisão de Cirurgia Pediátrica, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil, Divisão de Cirurgia Pediátrica, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Pereira, L.A.V. [Departamento de Histologia e Embriologia, Instituto de Biologia, Universidade Estadual de Campinas, UNICAMP, Campinas, SP, Brasil, Departamento de Histologia e Embriologia, Instituto de Biologia, Universidade Estadual de Campinas, UNICAMP, Campinas, SP (Brazil)

    2014-02-17

    Changes in vascular endothelial growth factor (VEGF) in pulmonary vessels have been described in congenital diaphragmatic hernia (CDH) and may contribute to the development of pulmonary hypoplasia and hypertension; however, how the expression of VEGF receptors changes during fetal lung development in CDH is not understood. The aim of this study was to compare morphological evolution with expression of VEGF receptors, VEGFR1 (Flt-1) and VEGFR2 (Flk-1), in pseudoglandular, canalicular, and saccular stages of lung development in normal rat fetuses and in fetuses with CDH. Pregnant rats were divided into four groups (n=20 fetuses each) of four different gestational days (GD) 18.5, 19.5, 20.5, 21.5: external control (EC), exposed to olive oil (OO), exposed to 100 mg nitrofen, by gavage, without CDH (N-), and exposed to nitrofen with CDH (CDH) on GD 9.5 (term=22 days). The morphological variables studied were: body weight (BW), total lung weight (TLW), left lung weight, TLW/BW ratio, total lung volume, and left lung volume. The histometric variables studied were: left lung parenchymal area density and left lung parenchymal volume. VEGFR1 and VEGFR2 expression were determined by Western blotting. The data were analyzed using analysis of variance with the Tukey-Kramer post hoc test. CDH frequency was 37% (80/216). All the morphological and histometric variables were reduced in the N- and CDH groups compared with the controls, and reductions were more pronounced in the CDH group (P<0.05) and more evident on GD 20.5 and GD 21.5. Similar results were observed for VEGFR1 and VEGFR2 expression. We conclude that N- and CDH fetuses showed primary pulmonary hypoplasia, with a decrease in VEGFR1 and VEGFR2 expression.

  10. Management of Fetal Bronchogenic Lung Cysts: A Case Report and Short Review of Literature

    Directory of Open Access Journals (Sweden)

    Ülkü Özmen Bayar

    2010-01-01

    Full Text Available Congenital malformations of the lung (CML are rare with similar embryological and clinical spectra and could result in mortality if left untreated. Bronchogenic cysts are formed during the budding of the tracheal diverticula and ventral foregut in the embryological period. In this paper we want to present a case of bronchogenic cyst with continuous intrauterine cyst aspiration follow-up. After the baby birth was operated and the postoperative period was uneventful. The pathological examination revealed a bronchogenic cyst.

  11. Combined measurement of fetal lung volume and pulmonary artery resistance index is more accurate for prediction of neonatal respiratory distress syndrome in preterm fetuses: A Pilot Study.

    Science.gov (United States)

    Laban, Mohamed; Mansour, Ghada; El-Kotb, Ahmed; Hassanin, Alaa; Laban, Zina; Saleh, Abdelrahman

    2017-10-02

    To estimate optimal cut-off values for mean fetal lung volume (FLV) and pulmonary artery resistance index (PA-RI) as noninvasive measures to predict neonatal respiratory distress syndrome (RDS) in preterm fetuses. A prospective study conducted at Ain Shams University Maternity Hospital, Egypt from May 2015 to July 2017: eighty eligible women diagnosed with preterm labor were recruited at 32-36 weeks' gestation. Before delivery, three-dimensional ultrasound was used to estimate FLV using virtual organ computer-aided analysis (VOCAL), while PA-RI was measured by Doppler ultrasonography. A total of 80 women were examined. 37 (46%) of the newborns developed neonatal RDS. FLV was significantly lower in neonates who developed RDS (p = 0.04), whereas PARI was significantly higher in those who didn't (p = 0.02). Cut-off values of FLV ≤ 27.2 cm(3) and PARI ≥ 0.77 predicted the subsequent development of RDS. Combining both cut-offs generated a more sensitive and specific methodical approach for the prediction of RDS (sensitivity 100%, specificity 88.5%). Measurement of FLV or PA-RI can predict RDS in preterm fetuses. Combined use of both measures bolstered their predictive significance.

  12. Plasticity of lung development in the amphibian, Xenopus laevis

    Directory of Open Access Journals (Sweden)

    Christopher S. Rose

    2013-10-01

    Contrary to previous studies, we found that Xenopus laevis tadpoles raised in normoxic water without access to air can routinely complete metamorphosis with lungs that are either severely stunted and uninflated or absent altogether. This is the first demonstration that lung development in a tetrapod can be inhibited by environmental factors and that a tetrapod that relies significantly on lung respiration under unstressed conditions can be raised to forego this function without adverse effects. This study compared lung development in untreated, air-deprived (AD and air-restored (AR tadpoles and frogs using whole mounts, histology, BrdU labeling of cell division and antibody staining of smooth muscle actin. We also examined the relationship of swimming and breathing behaviors to lung recovery in AR animals. Inhibition and recovery of lung development occurred at the stage of lung inflation. Lung recovery in AR tadpoles occurred at a predictable and rapid rate and correlated with changes in swimming and breathing behavior. It thus presents a new experimental model for investigating the role of mechanical forces in lung development. Lung recovery in AR frogs was unpredictable and did not correlate with behavioral changes. Its low frequency of occurrence could be attributed to developmental, physical and behavioral changes, the effects of which increase with size and age. Plasticity of lung inflation at tadpole stages and loss of plasticity at postmetamorphic stages offer new insights into the role of developmental plasticity in amphibian lung loss and life history evolution.

  13. Lung development of monotremes: evidence for the mammalian morphotype.

    Science.gov (United States)

    Ferner, Kirsten; Zeller, Ulrich; Renfree, Marilyn B

    2009-02-01

    The reproductive strategies and the extent of development of neonates differ markedly between the three extant mammalian groups: the Monotremata, Marsupialia, and Eutheria. Monotremes and marsupials produce highly altricial offspring whereas the neonates of eutherian mammals range from altricial to precocial. The ability of the newborn mammal to leave the environment in which it developed depends highly on the degree of maturation of the cardio-respiratory system at the time of birth. The lung structure is thus a reflection of the metabolic capacity of neonates. The lung development in monotremes (Ornithorhynchus anatinus, Tachyglossus aculeatus), in one marsupial (Monodelphis domestica), and one altricial eutherian (Suncus murinus) species was examined. The results and additional data from the literature were integrated into a morphotype reconstruction of the lung structure of the mammalian neonate. The lung parenchyma of monotremes and marsupials was at the early terminal air sac stage at birth, with large terminal air sacs. The lung developed slowly. In contrast, altricial eutherian neonates had more advanced lungs at the late terminal air sac stage and postnatally, lung maturation proceeded rapidly. The mammalian lung is highly conserved in many respects between monotreme, marsupial, and eutherian species and the structural differences in the neonatal lungs can be explained mainly by different developmental rates. The lung structure of newborn marsupials and monotremes thus resembles the ancestral condition of the mammalian lung at birth, whereas the eutherian newborns have a more mature lung structure.

  14. Development of a Guinea Pig Lung Deposition Model

    Science.gov (United States)

    2016-01-01

    Development of a Guinea Pig Lung Deposition Model Distribution Statement A. Approved for public release; distribution is unlimited. January...4 Figure 2. Particle deposition in the lung of the guinea pig via endotracheal breathing...Particle deposition in the lungs of guinea pigs via nasal breathing. ......................................... 12 v PREFACE The research work

  15. Timing and trajectories of fetal growth related to cognitive development in childhood.

    Science.gov (United States)

    von Ehrenstein, Ondine S; Mikolajczyk, Rafael T; Zhang, Jun

    2009-12-01

    The authors investigated timing and trajectories of fetal growth in relation to childhood development in the National Institute of Child Health and Human Development-Scandinavian Study of Successive Small-for-Gestational Age Births (1986-1988) (n = 1,059). Fetal size was assessed by ultrasound at 17, 25, and 33 gestational weeks and at birth. Bayley Scales of Infant Development and the Wechsler Preschool and Primary Scale of Intelligence-Revised tests were conducted at ages 1 and 5 years, respectively, producing mental and psychomotor development indexes and verbal and performance intelligence quotients. Relative fetal size was calculated as a standard deviation score at each data point; growth trajectories were explored with longitudinal mixture models. Fetal size at 17, 25, and 33 weeks was positively associated with mental development index; larger size at 33 weeks and at birth was associated with higher verbal intelligence quotient scores (2.61, 95% confidence interval: 1.06, 4.15 and 1.90, 95% confidence interval: 0.67, 3.13 increase per 1 standard deviation score, respectively); findings were similar for performance intelligence quotient. Seven trajectories were identified; scores were lower for "small" and "medium-to-small" trajectories than for "medium" and "big" (representing normal size) trajectories: mental development index (P development. Fetal growth trajectories may matter beyond birth.

  16. Transcriptional and Posttranscriptional Inhibition of Lysyl Oxidase Expression by Cigarette Smoke Condensate in Cultured Rat Fetal Lung Fibroblasts

    Science.gov (United States)

    Gao, Song; Chen, Keyang; Zhao, Yinzhi; Rich, Celeste B.; Chen, Lijun; Li, Sandy J.; Toselli, Paul; Stone, Phillip; Li, Wande

    2005-01-01

    Lysyl oxidase (LO) catalyzes crosslinking of collagen and elastin essential for maintaining the structural integrity of the lung extracellular matrix (ECM). To understand mechanisms of cigarette smoke (CS)-induced emphysema, we investigated effects of cigarette smoke condensate (CSC), the particulate matter of CS, on LO mRNA expression in cultured rat fetal lung fibroblasts (RFL6). Exposure of RFL6 cells to 0–120 μg CSC/ml for 24 h induced a dose-dependent inhibition of LO steady-state mRNAs, for example, reducing transcript levels to below 10% of the control in cells incubated with 80–120 μg CSC/ml. Nuclear run-on assays indicated a marked reduction in LO relative transcriptional rates amounting to 27.7% of the control in cells treated with 120 μg CSC/ml. The actinomycin D-chase assay showed that CSC enhanced the instability of LO transcripts. The t1/2 for LO mRNA decay was decreased from 24 h in the control to 4.5 h in cells treated with 120 μg CSC/ml. Moreover, 80–120 μg CSC/ml also inhibited LO promoter activity as revealed by suppression of reporter gene expression in cells transfected with LO promoter-luciferase vectors. Thus, inhibition of LO transcription initiation and enhancement of LO mRNA instability both contributed to downregulation of LO steady-state mRNA in CSC-treated cells. Note that inhibition of LO mRNA expression by CSC was closely accompanied by markedly decreased levels of transcripts of collagen type I and tropoelastin, two substrates of LO. Thus, transcriptional perturbation of LO and its substrates may be a critical mechanism for ECM damage in CS-induced emphysema. PMID:15933228

  17. Effects of Fetal Exposure to Asian Sand Dust on Development and Reproduction in Male Offspring.

    Science.gov (United States)

    Yoshida, Seiichi; Ichinose, Takamichi; Arashidani, Keiichi; He, Miao; Takano, Hirohisa; Shibamoto, Takayuki

    2016-11-23

    In recent experimental studies, we reported the aggravating effects of Asian sand dust (ASD) on male reproduction in mice. However, the effects of fetal ASD exposure on male reproduction have not been investigated. The present study investigated the effects of fetal ASD exposure on reproduction in male offspring. Using pregnant CD-1 mice, ASD was administered intratracheally on days 7 and 14 of gestation, and the reproduction of male offspring was determined at 5, 10, and 15 weeks after birth. The secondary sex ratio was significantly lower in the fetal ASD-exposed mice than in the controls. Histologic examination showed partial vacuolation of seminiferous tubules in immature mice. Moreover, daily sperm production (DSP) was significantly less in the fetal ASD-exposed mice than in the controls. DSP in the fetal ASD-exposed mice was approximately 10% less than the controls at both 5 and 10 weeks. However, both the histologic changes and the DSP decrease were reversed as the mice matured. These findings suggest that ASD exposure affects both the fetal development and the reproduction of male offspring. In the future, it will be necessary to clarify the onset mechanisms of ASD-induced male fetus death and male reproductive disorders.

  18. Study on features of female fetal reproductive system development in Chinese northeast fine-wool sheep

    Institute of Scientific and Technical Information of China (English)

    LIU Yunbo; ZHANG Guixue; HU Pengfei; HUANG He; ZHENG Peng; LI Wanhua

    2007-01-01

    Some charaterasics of female fetal reproductive system were studied in different gestation phases of Chinese northeast fine-wool sheep. The results showed that reproductive system consisted of ovary, oviduct, uterus and genitalia. The fetal ovaries were granular in early phase and became elliptic in later phase. The functional formula of ovarian weight, length and volume was obtained.Primary oocyte was encapsulated by monolayer cells in 7-week fetal ovary cortex. Primordial follicles were formed in 8-week fetal ovary, the follicular cells were sporadically arranged and not always regular. Complete organization of primordial follicles appeared until 10-week gestation, most of them scattered in nests in the following weeks of gestation. Two types of follicular complexes were found in fetal. There were continuous and quick mitosis of oogonia in fetal ovaries, large complexes were formed by oogoniaes encapsulated by multilayer of follicular cells, then they differentiated into small complexes, one or more primary oocytes were formed by mitosis of oogonia, primordial follicles which were caused by follicular cell approaching into them developed.

  19. Mitochondrial dysfunction and transactivation of p53-dependent apoptotic genes in BaP-treated human fetal lung fibroblasts.

    Science.gov (United States)

    Yang, Guangtao; Jiang, Ying; Rao, Kaimin; Chen, Xi; Wang, Qian; Liu, Ailin; Xiong, Wei; Yuan, Jing

    2011-12-01

    Benzo(a)pyrene (BaP) has been shown to be an inducer of apoptosis. However, mechanisms involved in BaP-induced mitochondrial dysfunction are not well-known. In this study, human fetal lung fibroblasts cells were treated with BaP (8, 16, 32, 64 and 128 μM) for 4 and 12 h. Cell viability, intracellular level of reactive oxygen species (ROS), total antioxidant capacity (T-AOC), mitochondrial membrane potential (ΔΨ(m)) and cytochrome c release were determined. Changes in transcriptional levels of p53-dependent apoptotic genes (p53, APAF1, CASPASE3, CASPASE9, NOXA and PUMA) were measured. At time point of 4 h, BaP induced the intracellular ROS generation in 64 (p BaP groups (p BaP groups (p BaP groups (p BaP group (p BaP groups (p BaP group a relatively little expression of p53 mRNA was observed (p BaP promoted the generation of excessive ROS and subsequently the mitochondrial depolarization, whereas transactivations of the p53-dependent apoptotic genes were significantly induced at the later period.

  20. Mapping fetal brain development in utero using magnetic resonance imaging: the Big Bang of brain mapping.

    Science.gov (United States)

    Studholme, Colin

    2011-08-15

    The development of tools to construct and investigate probabilistic maps of the adult human brain from magnetic resonance imaging (MRI) has led to advances in both basic neuroscience and clinical diagnosis. These tools are increasingly being applied to brain development in adolescence and childhood, and even to neonatal and premature neonatal imaging. Even earlier in development, parallel advances in clinical fetal MRI have led to its growing use as a tool in challenging medical conditions. This has motivated new engineering developments encompassing optimal fast MRI scans and techniques derived from computer vision, the combination of which allows full 3D imaging of the moving fetal brain in utero without sedation. These promise to provide a new and unprecedented window into early human brain growth. This article reviews the developments that have led us to this point, examines the current state of the art in the fields of fast fetal imaging and motion correction, and describes the tools to analyze dynamically changing fetal brain structure. New methods to deal with developmental tissue segmentation and the construction of spatiotemporal atlases are examined, together with techniques to map fetal brain growth patterns.

  1. Inflammation in the development of lung cancer: epidemiological evidence.

    Science.gov (United States)

    Engels, Eric A

    2008-04-01

    The lung is a site for repeated or chronic inflammatory insults. Epidemiologic research has provided evidence to support the hypothesis that tissue damage caused by inflammation can initiate or promote the development of lung cancer, possibly in conjunction with tobacco use. For example, some studies suggest an increased risk of lung cancer among persons with lung infections, such as tuberculosis, bacterial pneumonia, or inflammatory lung diseases. Elevated serum levels of C-reactive protein, an inflammation marker, are associated with heightened lung cancer risk. Recent studies also demonstrate increased lung cancer risk among immunosuppressed individuals infected with HIV. Other research indicates an association between genetic polymorphisms in the inflammation pathway, which might modulate the inflammatory response and lung cancer risk.

  2. Consequences of a Maternal High-Fat Diet and Late Gestation Diabetes on the Developing Rat Lung

    OpenAIRE

    Michelle L Baack; Forred, Benjamin J.; Larsen, Tricia D.; Jensen, Danielle N.; Wachal, Angela L.; Khan, Muhammad Ali; Vitiello, Peter F.

    2016-01-01

    Rationale Infants born to diabetic or obese mothers are at risk of respiratory distress and persistent pulmonary hypertension of the newborn (PPHN), conceivably through fuel-mediated pathogenic mechanisms. Prior research and preventative measures focus on controlling maternal hyperglycemia, but growing evidence suggests a role for additional circulating fuels including lipids. Little is known about the individual or additive effects of a maternal high-fat diet on fetal lung development. Objec...

  3. In vitro characteristics of pulmonary neuroendocrine cells isolated from rabbit fetal lung. I. Effects of culture media and nerve growth factor.

    Science.gov (United States)

    Cutz, E; Yeger, H; Wong, V; Bienkowski, E; Chan, W

    1985-12-01

    Pulmonary neuroendocrine (NE) cells, dispersed throughout the airway mucosa as single cells and as innervated clusters (neuroepithelial bodies), were isolated from rabbit fetal lung and studied in short-term culture. The effects of culture media and nerve growth factor (NGF) on in vitro maintenance, differentation, and cell kinetics of isolated NE cells were examined. For demonstration of NE cells in intact lung, during cell separation and after culture, immunostaining for serotonin, formaldehyde-induced fluorescence method, histochemical reaction for acetylcholinesterase, and electron microscopy were used. The isolation procedure consisted of mechanical and enzymatic dissociation of lung tissue followed by separation of isolated cells on a discontinuous gradient of Percoll, resulting in 5- to 10-fold enrichment in NE cells. Cell fractions enriched in NE cells were cultured up to 7 days either in supplemented alpha-minimal essential medium with fetal bovine serum or in defined, hormone-supplemented, serum-free medium. NGF (2.5 S 5 to 50 ng/ml) was added to both serum-supplemented and serum-free media; cultures without NGF served as control. The number of serotonin-immunoreactive NE cells maintained in serum-supplemented medium (0.5% fetal bovine serum) increased significantly (p less than 0.05) on days 4 and 7 compared with cultures grown in serum-free medium. NE cells maintained in serum-supplemented medium incorporated [3H]thymidine and their labeling index was significantly increased (p less than 0.01) on day 7, whereas few or no NE cells were labeled in cultures grown in serum-free medium. NGF had no effect on the maintenance or kinetics of NE cells. Cultured NE cells formed elongated (unipolar or bipolar) neurite-like cytoplasmic processes with a button-like ending, regardless of the presence of NGF. Amine accumulated in perinuclear cytoplasm and in button-like endings. Staining for acetylcholinesterase (strongly positive in intact neuroepithelial bodies) was

  4. 孕期亚临床维生素A缺乏对胎鼠肺形态发育的影响%Effects of marginal vitamin A deficiency during pregnancy on the lung morphology of fetal rats

    Institute of Scientific and Technical Information of China (English)

    刘友红

    2012-01-01

    (RT-PCR), then the values of RAR mRNAs were compared to glyceraldehyde-3-phos-phate dehydrogenase(GAPDH)mRNA. [Results] 1 )The weights of fetals'body.lung and liver in VAN group were higher than those of MVAD group(P<0. 05). 2)By light microscopeChigh and lower power lens),the fetal lung morphology were better developed in VAN group than MVAD group. In VAN group,alveolar-like structure were better-arranged,and alveolar septums were thinner. They were rich in blood capillary among the interstitial tissue. They were canalicular period; but MVAD group were gland period. 3)Compared with the two groups, the vitamin A concentrations of lungs in VAN group were higher than those of MVAD group(P<0.05). 4)The levels of RAR and mRNA in VAN group were lower than those of MVAD group(P<0.05). [Conclusions] The weights of fetals' body,lung and liver,the fetal lung morphology,the vitamin A concentrations of lungs and the levels of RAR and mRNA are all influenced by vitamin A level during pregnancy. The fetal lung whose mother are vitamin A deficiency during pregnancy are worse developed.

  5. Studies of some correlations of ovaries with corpora lutea and fetal development in female Nelore cows

    Directory of Open Access Journals (Sweden)

    Renata Barbieri Trevisan

    2012-06-01

    Full Text Available This study evaluated the right and left ovaries of 30 pregnant Nelore cows. The reproductive tracts were collected at slaughterhouses in the western region of the state of São Paulo, and the study was conducted at the Laboratório de Anatomia Animal at UNESP (in Araçatuba. The size (occipitosacral length, height and weight of the fetuses were analyzed. The length, width and thickness (using calipers of the ovaries and corpora lutea, and weight and volume of the gonads were also measured. The data related to the ovaries and corpora lutea were correlated with fetal development, using a SAS program to analyze the Pearson correlation coefficient, and adjusted using a simple linear regression model. There was a significant correlation between the right ovary variables and fetal development; positive for width and negative for thickness. For the corpora lutea and fetal development, there was a significant negative correlation with the volume.

  6. Development of Fetal Movement between 26 and 36-Weeks' Gestation in Response to Vibro-Acoustic Stimulation.

    Science.gov (United States)

    Grant-Beuttler, Marybeth; Glynn, Laura M; Salisbury, Amy L; Davis, Elysia Poggi; Holliday, Carol; Sandman, Curt A

    2011-01-01

    Ultrasound observation of fetal movement has documented general trends in motor development and fetal age when motor response to stimulation is observed. Evaluation of fetal movement quality, in addition to specific motor activity, may improve documentation of motor development and highlight specific motor responses to stimulation. The aim of this investigation was to assess fetal movement at 26 and 36-weeks gestation during three conditions (baseline, immediate response to vibro-acoustic stimulation (VAS), and post-response). A prospective, longitudinal design was utilized. Twelve normally developing fetuses, eight females and four males, were examined with continuous ultrasound imaging. The fetal neurobehavioral coding system (FENS) was used to evaluate the quality of motor activity during 10-s epochs over the three conditions. Seventy-five percent of the fetuses at the 26-week assessment and 100% of the fetuses at the 36-week assessment responded with movement immediately following stimulation. Significant differences in head, fetal breathing, general, limb, and mouthing movements were detected between the 26 and 36-week assessments. Movement differences between conditions were detected in head, fetal breathing, limb, and mouthing movements. Smoother and more complex movement was observed with fetal maturation. Following VAS stimulation, an immediate increase of large, jerky movements suggests instability in fetal capabilities. Fetal movement quality changes over gestation may reflect sensorimotor synaptogenesis in the central nervous system, while observation of immature movement patterns following VAS stimulation may reflect movement pattern instability.

  7. Development of Fetal Movement between 26 and 36 Weeks’ Gestation in Response to Vibro-acoustic Stimulation

    Directory of Open Access Journals (Sweden)

    Marybeth eGrant-Beuttler

    2011-12-01

    Full Text Available Background: Ultrasound observation of fetal movement has documented general trends in motor development and fetal age when motor response to stimulation is observed. Evaluation of fetal movement quality, in addition to specific motor activity, may improve documentation of motor development and highlight specific motor responses to stimulation. Aims: The aim of this investigation was to assess fetal movement at 26 and 36 weeks gestation during three conditions (baseline, immediate response to vibro-acoustic stimulation (VAS, and post-response. Design: A prospective, longitudinal design was utilized. Subjects: Twelve normally developing fetuses, 8 females and 4 males, were examined with continuous ultrasound imaging. Outcome measures: The Fetal Neurobehavioral Coding System (FENS was used to evaluate the quality of motor activity during 10-second epochs over the three conditions. Results: Seventy-five percent of the fetuses at the 26 week assessment and 100% of the fetuses at the 36 week assessment responded with movement immediately following stimulation. Significant differences in head, fetal breathing, general, limb, and mouthing movements were detected between the 26 week and 36 week assessments. Movement differences between conditions were detected in head, fetal breathing, limb, and mouthing movements. Conclusions: Smoother and more complex movement was observed with fetal maturation. Following VAS stimulation, an immediate increase of large, jerky movements suggest instability in fetal capabilities. Fetal movement quality changes over gestation may reflect sensorimotor synaptogenesis in the central nervous system, while observation of immature movement patterns following VAS stimulation may reflect movement pattern instability.

  8. Development of Fetal Movement between 26 and 36-Weeks’ Gestation in Response to Vibro-Acoustic Stimulation

    Science.gov (United States)

    Grant-Beuttler, Marybeth; Glynn, Laura M.; Salisbury, Amy L.; Davis, Elysia Poggi; Holliday, Carol; Sandman, Curt A.

    2011-01-01

    Background: Ultrasound observation of fetal movement has documented general trends in motor development and fetal age when motor response to stimulation is observed. Evaluation of fetal movement quality, in addition to specific motor activity, may improve documentation of motor development and highlight specific motor responses to stimulation. Aim: The aim of this investigation was to assess fetal movement at 26 and 36-weeks gestation during three conditions (baseline, immediate response to vibro-acoustic stimulation (VAS), and post-response). Design: A prospective, longitudinal design was utilized. Subjects: Twelve normally developing fetuses, eight females and four males, were examined with continuous ultrasound imaging. Outcome Measures: The fetal neurobehavioral coding system (FENS) was used to evaluate the quality of motor activity during 10-s epochs over the three conditions. Results: Seventy-five percent of the fetuses at the 26-week assessment and 100% of the fetuses at the 36-week assessment responded with movement immediately following stimulation. Significant differences in head, fetal breathing, general, limb, and mouthing movements were detected between the 26 and 36-week assessments. Movement differences between conditions were detected in head, fetal breathing, limb, and mouthing movements. Conclusion: Smoother and more complex movement was observed with fetal maturation. Following VAS stimulation, an immediate increase of large, jerky movements suggests instability in fetal capabilities. Fetal movement quality changes over gestation may reflect sensorimotor synaptogenesis in the central nervous system, while observation of immature movement patterns following VAS stimulation may reflect movement pattern instability. PMID:22207855

  9. Improving metabolic health in obese male mice via diet and exercise restores embryo development and fetal growth.

    Directory of Open Access Journals (Sweden)

    Nicole O McPherson

    Full Text Available Paternal obesity is now clearly associated with or causal of impaired embryo and fetal development and reduced pregnancy rates in humans and rodents. This appears to be a result of reduced blastocyst potential. Whether these adverse embryo and fetal outcomes can be ameliorated by interventions to reduce paternal obesity has not been established. Here, male mice fed a high fat diet (HFD to induce obesity were used, to determine if early embryo and fetal development is improved by interventions of diet (CD and/or exercise to reduce adiposity and improve metabolism. Exercise and to a lesser extent CD in obese males improved embryo development rates, with increased cell to cell contacts in the compacting embryo measured by E-cadherin in exercise interventions and subsequently, increased blastocyst trophectoderm (TE, inner cell mass (ICM and epiblast cell numbers. Implantation rates and fetal development from resulting blastocysts were also improved by exercise in obese males. Additionally, all interventions to obese males increased fetal weight, with CD alone and exercise alone, also increasing fetal crown-rump length. Measures of embryo and fetal development correlated with paternal measures of glycaemia, insulin action and serum lipids regardless of paternal adiposity or intervention, suggesting a link between paternal metabolic health and subsequent embryo and fetal development. This is the first study to show that improvements to metabolic health of obese males through diet and exercise can improve embryo and fetal development, suggesting such interventions are likely to improve offspring health.

  10. Diagnosis of the human fetal age based on the development of the normal kidney

    Directory of Open Access Journals (Sweden)

    Lizardo-Daudt Helena Maria

    2002-01-01

    Full Text Available Background and aims: The diagnosis of human fetal age is usually estimated based on the measurement of crown-rump length or crown-heel length and the weight of the fetus. However, this estimate is not totally accurate and sometimes is necessary to combine other data to determine the fetal age. An analysis of the normal embryological development of the kidney may assist in this determination. The histology of this process, although well described, lacks photographic documentation. We intend to fill this gap by providing histologists and pathologists, especially inexperienced ones, with information about the staging of the renal development through microphotography. The objective of the present study was to achieve greater accuracy for the diagnosis of human fetal age through the proposed classification and the photographic documentation presented. Material and methods: Normal embryological development of the human kidney was studied by light microscopy. The fetal period from 6 to 40 weeks of gestation was observed according the stage of maturity of glomeruli and tubules; localization of glomeruli, occurrence of nephrogenic tissue and cortico-medullary differentiation. At least 5 different exams were observed from each week of development. Two hundred four exams were analyzed in the whole study. The histological characteristics were quantified and the process was documented by microphotography. Results and final considerations: The fetal development of the kidney was divided into 8 stages, which was documented through microphotography. Nephron structural formation occurred until the 34th week of prenatal development. From the 35th week on, tubules and glomeruli continued to mature without the formation of new nephrons. The proposed classification intends to improve the accuracy of the fetal age diagnosis.

  11. A Probability Analysis of Historical Pregnancy and Fetal Data from Dutch Belted and New Zealand White Rabbit Strains from Embryo-Fetal Development Studies.

    Science.gov (United States)

    Posobiec, Lorraine M; Cox, Estella M; Solomon, Howard M; Lewis, Elise M; Wang, Kai-fen; Stanislaus, Dinesh

    2016-04-01

    Embryo-fetal development (EFD) studies, typically in pregnant rats and rabbits, are conducted prior to enrolling females of reproductive age in clinical trials. Common rabbit strains used are the New Zealand White (NZW) and Dutch Belted (DB). As fetal abnormalities can occur in all groups, including controls, Historical Control Data (HCD) is compiled using data from control groups of EFD studies, and is used along with each study's concurrent control group to help determine whether fetal abnormalities are caused by the test article or are part of background incidences. A probability analysis was conducted on 2014 HCD collected at Charles River Inc., Horsham PA on Covance NZW, Covance DB, and Charles River (CR) NZW rabbits. The analysis was designed to determine the probability of 2 or 3 out of a group of 22 does aborting their litter or of having a fetal abnormality by chance. Results demonstrate that pregnancy parameters and fetal observations differ not only between strains, but between sources of rabbits of the same strain. As a result the probability of these observations occurring by chance in two or three litters was drastically different. Although no one single strain is perfect, this analysis highlights the need to appreciate the inherent differences in pregnancy and fetal abnormalities between strains, and points out that an apparent isolated increased incidence of an observation in one strain will not necessarily be test-article related in another strain. A robust HCD is critical for interpretation of EFD rabbit studies, regardless of the rabbit strain used.

  12. Biphasic changes in fetal heart rate variability in preterm fetal sheep developing hypotension after acute on chronic lipopolysaccharide exposure.

    Science.gov (United States)

    Lear, Christopher A; Davidson, Joanne O; Booth, Lindsea C; Wassink, Guido; Galinsky, Robert; Drury, Paul P; Fraser, Mhoyra; Bennet, Laura; Gunn, Alistair J

    2014-08-15

    Perinatal exposure to infection is highly associated with adverse outcomes. Experimentally, acute, severe exposure to gram-negative bacterial lipopolysaccharide (LPS) is associated with increased fetal heart rate variability (FHRV). It is unknown whether FHRV is affected by subclinical infection with or without acute exacerbations. We therefore tested the hypothesis that FHRV would be associated with hypotension after acute on chronic exposure to LPS. Chronically instrumented fetal sheep at 0.7 gestation were exposed to a continuous low-dose LPS infusion (n = 12, 100 ng/kg over 24 h, followed by 250 ng·kg(-1)·24 h(-1) for a further 96 h) or the same volume of saline (n = 10). Boluses of either 1 μg LPS or saline were given at 48, 72, and 96 h. Low-dose infusion was not associated with hemodynamic or FHRV changes. The first LPS bolus was associated with tachycardia and suppression of nuchal electromyographic activity in all fetuses. Seven of twelve fetuses developed hypotension (a fall in mean arterial blood pressure ≥5 mmHg). FHRV was transiently increased only at the onset of hypotension, in association with increased cytokine induction and electroencephalogram suppression. FHRV then fell before the nadir of hypotension, with transient suppression of short-term FHRV. After the second LPS bolus, the hypotension group showed a biphasic pattern of a transient increase in FHRV followed by more prolonged suppression. These findings suggest that infection-related hypotension in the preterm fetus mediates the transient increase in FHRV and that repeated exposure to LPS leads to progressive loss of FHRV.

  13. Heterogeneity of serum lipoproteins during the fetal and neonatal development of the pig.

    Science.gov (United States)

    Johansson, M B

    1984-01-01

    Serum lipoproteins from fetal, neonatal and adult pigs were characterized with the use of lipid analysis, polyacrylamide gradient gel electrophoresis, two-dimensional immunoelectrophoresis and zonal ultracentrifugation. Almost all serum cholesterol was found in LDL during the early stages of fetal development, while low but increasing levels appeared in the fetal pig HDL by the end of the gestation period. In the fetal pig, most of the serum triglycerides could be found in the HDL fraction. After the start of suckling, the levels of serum triglycerides and cholesterol increased. Most of these exogenous lipids were found in the chylomicrons + VLDL + LDL fraction of the newborn pig serum. The molecular weights of the native serum lipoproteins were calculated as being 2.0-2.4 X 10(5) daltons for newborn pig HDL and 1.4-1.7 X 10(6) daltons for newborn pig LDL. Minor changes in the molecular weight distributions were detected within these ranges for both HDL and LDL during fetal and neonatal development of the pig. Zonal ultracentrifugation of neonatal pig serum partly separated the LDL into three subfractions, whereas neonatal HDL appeared as one broad fraction.

  14. Effects of a 4.7 T static magnetic field on fetal development in ICR mice

    Energy Technology Data Exchange (ETDEWEB)

    Okazaki, Ryuji; Ootsuyama, Akira; Uchida, Soshi; Norimura, Toshiyuki [Univ. of Occupational and Environmental Health, Kitakyushu, Fukuoka (Japan). School of Medicine

    2001-09-01

    In order to determine the effects of a 4.7 T static magnetic field (SMF) on fetal development in mice, we evaluated fetal teratogenesis and endochondral ossification following exposure in utero. Pregnant ICR mice were exposed to a 4.7 T SMF from day 7.5 to 9.5 of gestation in a whole-body dose, and sacrificed on day 18.5 of gestation. We examined with incidence of prenatal death, external malformations and fetal skeletal malformations. There were no significant differences observed in the incidence of prenatal death and/or malformations between SMF-exposed mice and control mice. Further, we evaluated the immunoreactivity for the vascular endothelial growth factor (VEGF), which is implicated in angiogenesis and osteogenesis, in the sternum of fetal mice following magnetic exposure. Our studies also indicated that on day 16.5 of gestation following SMF exposure, the immunoreactivity for VEGF was increased compared to unexposed controls. However, it was decreased in the exposed group compared to the control group on day 18.5 of gestation. DNA and proteoglycan (PG) synthesis were also measured in rabbit costal growth plate chondrocytes in vitro. No significant differences were observed in DNA synthesis between the SMF exposed chondrocytes and the control chondrocytes; however, PG synthesis in SMF exposed chondrocytes increased compared to the controls. Based on these results, we suggest that while SMF exposure promoted the endochondral ossification of chondrocytes, it did not induce any harmful effects on fetal development in ICR mice. (author)

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

    Science.gov (United States)

    Wedekind, Lauren; Belkacemi, Louiza

    2016-01-01

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

  16. Pluripotent stem cells exhibiting similar characteristics can be isolated from human fetal bone marrow,heart,liver,muscle,lung,derma,kidney,and fat

    Institute of Scientific and Technical Information of China (English)

    FANG Baijun; SONG Yongping; ZHAO Chunhua; SHI Mingxia; LIN Quande

    2007-01-01

    Previously,we reported that a cell population derived from human fetal bone marrow fBM),termed here Flk1+CD34-postembryonic pluripotent stem cells(PPSCs)that have the characteristics of mesenchymal stem cells (MSCs),could difierentiate into ectodermal,endodermal and mesodermal celI types at the single cell level in vitro,and that these cells could also difierentiate into the epithelium of liver,lung,gut,as well as the hematopoietic and endothelial lineages after transplantion into irradiated non-obese diabetic/severe combined immunodeficient(NOD/SCID) mice.In this study,we further isolated pluripotent stem cells from human fetal heart,liver,muscle,lung,derma,kidney,and fat and then analyzed the characteristics and function of these stem cells.It was found that the phenotype of the culture-expanded pluripotent stem cells from different fetal tissues was similar to BM-derived Flk1+CD34-PPSCs.i.e.Flk1 and CD44 positive,GlyA,CD34,CD45,class I-HLA and HLA-DR negative.Morphologically,these cells were fibroblast-like and the doubling time was about 30 h.More importantly,culture-expanded pluripotent stem cells from all these fetal tissues were able to differentiate into cells with morphologic and phenotypic characteristics of adipocytes,osteocytes,neurons,gilal cells and hepatocytes.These pluripotent stem cells with characteristics similar to fetal BM-derived Flk1+CD34-PPSCs can be selected and cultured from tissues other than the BM.This phenomenon may help explain the"stem cell plasticity"found in multiple human tissues.In addition,as fetal BM-derived Flk1+CD34-PPSCs,these pluripotent stem cells from different fetal tissues had the capacity for self-renewal and multi-lineage difierentiation even after being expanded for more than 40 population doublings in vitro.Thus,they may be an ideal source of stem cells for treatment of inherited or degenerative diseases.

  17. Ectopic expression of C/EBPalpha in the lung epithelium disrupts late lung development.

    Science.gov (United States)

    Berg, Tove; Didon, Lukas; Nord, Magnus

    2006-10-01

    The lung develops from the endoderm through a process of branching morphogenesis. This process is highly active during the pseudoglandular stage of lung development and continues into the canalicular stage, resulting in the formation of terminal sacs. CCAAT/enhancer binding proteins (C/EBPs) are transcription factors regulating central aspects of differentiation and proliferation. We report here the developmental expression of C/EBPalpha, -beta, and -delta in the lung. C/EBPalpha exhibits a dynamic expression pattern and is first detected during the late pseudoglandular stage. At this stage, expression is observed in a subset of epithelial cells in the distal parts of the branching tubules. The expression of C/EBPalpha is confined to nonproliferating cells. To examine the role of C/EBPalpha in lung development, we generated transgenic mice ectopically expressing C/EBPalpha in the lung epithelium using the human surfactant protein C promoter. Lungs from these mice were of normal size but exhibited a phenotype characterized by fewer and larger developing epithelial tubules, indicating that the branching process was affected. No effects on overall proliferation or cellular differentiation were observed. When this phenotype was compared with that of mice carrying a targeted mutation of the Cebpa gene, the Cebpa-/- mice exhibited a similar developmental phenotype. In conclusion, our results show a role for C/EBPalpha in lung development and suggest a function in the later stages of lung branching morphogenesis.

  18. Effects of 2-chlorodibenzofuran on fetal development in mice

    Energy Technology Data Exchange (ETDEWEB)

    Usami, Makoto; Sakemi, Kazue; Tabata, Hirobumi; Kawashima, Kunio; Takanaka, Akira [National Institute of Hygienic Sciences, Tokyo (Japan)

    1993-11-01

    2-Chlorodibenzofuran (2-MCDF), a monochlorinated derivative of dibenzofuran, has been detected as a contaminant in chlorinated tap water in Japan. Shiraishi et al. (1985) analyzed polynuclear aromatic hydrocarbons in Tsukuba tap water and detected 0.04-1.4 ng/L of 2-MCDF. This means that unintended human exposure to 2-MCDF has occurred, and therefore safety evaluation of 2-MCDF is needed. Toxicological information on 2-MCDF is limited and available only on mutagenicity and metabolic fate. In the Ames test, 2-MCDF showed weak mutagenic activity on Salmonella typhimurium strain TA 98 above 0.4 {mu}mol/plate, but not on strain TA 100 even at 10 {mu}mol/plate, and this activity was diminished by the addition of S9 mix. After intravenous or oral administration to rats, 2-MCDF is rapidly metabolized and excreted in bile and urine. Major metabolites in the rate bile fluid were 2- and/or 7-hydroxylated forms of 2-MCDF. For developmental toxicity, we previously examined the embryotoxicity of 2-MCDF by using post-implantation rat embryo culture. When day 9 embryos were continuously exposed throughout 48 hr culture period either in the presence or in the absence of a metabolic activation system, 2-MCDF at 1 mM was embryotoxic and caused morphological abnormalities of the embryos. However, dosing of up to 1000 mg/kg/day of 2-MCDF to pregnant rats during days 9 to 11 of gestation, corresponding to the culture period, had no effects on the embryo-fetal growth. It was tentatively concluded from these results that 2-MCDF had weak-inactive teratogenicity in rats. In the present study, we further examined fetal effects of 2-MCDF by a teratogenicity test in which the dosing period covers the major organogenic period. We used mice, since they have been used for the evaluation of teratogenicity of polychlorinated congeners of 2-MCDF, because of their higher susceptibility than that of rats. 16 refs., 1 fig., 3 tabs.

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

    Science.gov (United States)

    Blackburn, Daniel G; Flemming, Alexander F

    2009-09-15

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

  20. Effect of IFN-γ and dexamethasone on TGF-β1-induced human fetal lung fibroblast-myofibroblast differentiation

    Institute of Scientific and Technical Information of China (English)

    LiGU; Yuan-jueZHU; Zi-jianGUO; Xing-xiangXU; Wen-bingXU

    2004-01-01

    AIM: To study whether Smads signaling pathway was involved in human fetal lung fibroblast-myofibroblast differentiation induced by transforming growth factor (TGF)-β1 and the role of interferon (IFN)-γ, dexamethasone (DEX) in the fibroblast-myofibroblast differentiation. METHODS: α-Smooth muscle actin (α-SMA), Smad2/3, and Smad7 protein were assessed by Western blot. Collagen protein was analyzed by measuring hydroxyproline, α-SMA and collagen III mRNA were assessed by RT-PCR. Myofibroblasts morphology and Smad2/3 nuclear translocation were assessed by immunohistochemistry. The overexpression of Smad7, a negative mediator of Smads signaling pathway, was acquired by transfection of Smad7 vector. RESULTS: During fibroblast-myofibroblast differentiation induced by TGF-β1, IFN-γ 200 μg/L markedly blocked TGF-β1-induced α-SMA protein expression (PO.05) and collagen protein (P>0.05) and mRNA expression (P>0.05) and did not change myofibroblasts morphology. Transient transfection of Smad7 vector resulted in significant inhibition of TGF-β1-induced α-SMA expression (P<0.01). IFN-γ 200 μg/L did not block TGF-β1-stimulated Smad2/3 phosphorylation and their nuclear translocation. CONCLUSION: TGF-131 induced fibroblastmyofibroblast differentiation in a Smad proteins-dependent manner. IFN-γ could block this process but it was not mediated by interrupting smad2/3 phosphorylation and their nuclear translocation and DEX played a synergism withTGF-β1. Differentiated myofibroblasts, however, were resistant to both IFN-γ and DEX.

  1. Testing the Fetal Origins Hypothesis in a developing country: evidence from the 1918 Influenza Pandemic.

    Science.gov (United States)

    Nelson, Richard E

    2010-10-01

    The 1918 Influenza Pandemic is used as a natural experiment to test the Fetal Origins Hypothesis. This hypothesis states that individual health as well as socioeconomic outcomes, such as educational attainment, employment status, and wages, are affected by the health of that individual while in utero. Repeated cross sections from the Pesquisa Mensal de Emprego (PME), a labor market survey from Brazil, are used to test this hypothesis. I find evidence to support the Fetal Origins Hypothesis. In particular, compared to individuals born in the few years surrounding the Influenza Pandemic, those who were in utero during the pandemic are less likely to be college educated, be employed, have formal employment, or know how to read and have fewer years of schooling and a lower hourly wage. These results underscore the importance of fetal health especially in developing countries.

  2. [Morphogenesis of Human Fetal Thymus during Weeks 22-27 of Development].

    Science.gov (United States)

    Kulida, L V; Peretyatko, L P; Nazarov, S B

    2015-01-01

    Distinctive features of human fetal thymus morphogenesis in early ontogeny in the case of uncomplicated pregnancy have been characterized. A steady increase of thymus dimensions and weight occurred concomitantly to differentiation of morphofunctional zones within the organ. Cell differentiation in the subcapsular and inner cortical zones of the thymus lobes was manifested as changes in parameters of expression of T-lymphocyte antigens CD1, CD2, and CD3 and ultrastructural features of reticuloepithelial cells (REC) type I and II forming a microenvironment for lymphocytes. RECs of the medullar zone formed a glomerular syncytium with desmosomal interepithelial contacts by week 22 of fetal development. Small lymphocytes predominated among thymocytes (66%). Hassall's corpuscles, the structural correlates of morphological and functional maturity, predominated in the fetal thymuses during developmental weeks 25-27.

  3. Development of coagulation regulatory proteins in the fetal and neonatal lamb.

    Science.gov (United States)

    Manco-Johnson, Marilyn J; Jacobson, Linda J; Hacker, Michele R; Townsend, Susan F; Murphy, James; Hay, William

    2002-10-01

    To investigate the development of coagulation regulatory proteins-protein C (PC), protein S (PS), and antithrombin (AT)-in relationship to the procoagulant protein factor X (FX), a chronically catheterized fetal ovine model was used. Infusion and sampling catheters were placed into pregnant ewes and their fetuses and maintained from mid-gestation. From a total of 110 fetuses, 17 lambs, and 63 ewes that were studied on one to 15 occasions, 212 fetal, 88 neonatal, and 157 maternal samples were obtained. Liver tissue was obtained from 31 fetuses and 15 ewes. Plasma levels of all proteins studied were higher in the ewe than in the fetus (p 0.05). This study suggests that fetal regulation of coagulation proteins follows characteristic patterns relative to the vitamin K dependence of the protein rather than its role as a procoagulant versus regulatory protein.

  4. WHO multicentre study for the development of growth standards from fetal life to childhood

    DEFF Research Database (Denmark)

    Merialdi, Mario; Widmer, Mariana; Gülmezoglu, Ahmet Metin

    2014-01-01

    both for clinical and scientific reasons. The currently used fetal growth references are derived mainly from North American and European population and may be inappropriate for international use, given possible variances in the growth rates of fetuses from different ethnic population groups. WHO has...... ten developing and industrialized countries: Argentina, Brazil, Democratic Republic of Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand. At each centre, 140 pregnant women will be recruited between 8 + 0 and 12 + 6 weeks of gestation. Subsequently, visits for fetal biometry...

  5. Antibody repertoire development in fetal and neonatal piglets XXI. Usage of most VH genes remains constant during fetal and postnatal development.

    Science.gov (United States)

    Butler, John E; Sun, Xuizhu; Wertz, Nancy; Lager, Kelly M; Chaloner, Kathryn; Urban, Joseph; Francis, David L; Nara, Peter L; Tobin, Gregory J

    2011-12-01

    Usage of variable region gene segments during development of the antibody repertoire in mammals is unresolved in part because of the complexity of the locus in mice and humans and the difficulty of distinguishing intrinsic from extrinsic influences in these species. We present the first vertical studies on VH usage that spans the fetal and neonatal period using the piglet model. We tracked VH usage in DNA rearrangements and in VDJ transcripts throughout 75 days of gestation (DG) in outbred fetuses, thereafter in outbred germfree and colonized isolator piglets, isolator piglets infected with swine influenza and in conventionally reared nematode-infected adults. Seven VH genes account for >90% of the pre-immune repertoire which is the same among tissues and in both transcripts and DNA rearrangements. Statistical modeling supports the view that proportional usage of the major genes remains constant during fetal life and that postnatal usage ranking is similar to that during fetal life. Changes in usage ranking are developmental not antigen dependent. In this species exposure to environmental antigens results in diversification of the repertoire by somatic hypermutation of the same small number of VH genes that comprise the pre-immune repertoire, not by using other VH gene available in the germline. Therefore in swine a small number of VH genes shape the antibody repertoire throughout life questioning the need for extensive VH polygeny.

  6. Paternal Low Protein Diet Programs Preimplantation Embryo Gene Expression, Fetal Growth and Skeletal Development in Mice.

    Science.gov (United States)

    Watkins, Adam J; Sirovica, Slobodan; Stokes, Ben; Isaacs, Mark; Addison, Owen; Martin, Richard A

    2017-02-08

    Defining the mechanisms underlying the programming of early life growth is fundamental for improving adult health and wellbeing. While the association between maternal diet, offspring growth and adult disease risk is well-established, the effect of father's diet on offspring development are largely unknown. Therefore, we fed male mice an imbalanced low protein diet (LPD) to determine the impact on post-fertilisation development and fetal growth. We observed that in preimplantation embryos derived from LPD fed males, expression of multiple genes within the central metabolic AMPK pathway was reduced. In late gestation, paternal LPD programmed increased fetal weight, however, placental weight was reduced, resulting in an elevated fetal:placental weight ratio. Analysis of gene expression patterns revealed increased levels of transporters for calcium, amino acids and glucose within LPD placentas. Furthermore, placental expression of the epigenetic regulators Dnmt1 and Dnmt3L were increased also, coinciding with altered patterns of maternal and paternal imprinted genes. More strikingly, we observed fetal skeletal development was perturbed in response to paternal LPD. Here, while offspring of LPD fed males possessed larger skeletons, their bones comprised lower volumes of high mineral density in combination with reduced maturity of bone apatite. These data offer new insight in the underlying programming mechanisms linking poor paternal diet at the time of conception with the development and growth of his offspring.

  7. Complex epithelial remodeling underlie the fusion event in early fetal development of the human penile urethra.

    Science.gov (United States)

    Shen, Joel; Overland, Maya; Sinclair, Adriane; Cao, Mei; Yue, Xuan; Cunha, Gerald; Baskin, Laurence

    We recently described a two-step process of urethral plate canalization and urethral fold fusion to form the human penile urethra. Canalization ("opening zipper") opens the solid urethral plate into a groove, and fusion ("closing zipper") closes the urethral groove to form the penile urethra. We hypothesize that failure of canalization and/or fusion during human urethral formation can lead to hypospadias. Herein, we use scanning electron microscopy (SEM) and analysis of transverse serial sections to better characterize development of the human fetal penile urethra as contrasted to the development of the human fetal clitoris. Eighteen 7-13 week human fetal external genitalia specimens were analyzed by SEM, and fifteen additional human fetal specimens were sectioned for histologic analysis. SEM images demonstrate canalization of the urethral/vestibular plate in the developing male and female external genitalia, respectively, followed by proximal to distal fusion of the urethral folds in males only. The fusion process during penile development occurs sequentially in multiple layers and through the interlacing of epidermal "cords". Complex epithelial organization is also noted at the site of active canalization. The demarcation between the epidermis of the shaft and the glans becomes distinct during development, and the epithelial tag at the distal tip of the penile and clitoral glans regresses as development progresses. In summary, SEM analysis of human fetal specimens supports the two-zipper hypothesis of formation of the penile urethra. The opening zipper progresses from proximal to distal along the shaft of the penis and clitoris into the glans in identical fashion in both sexes. The closing zipper mechanism is active only in males and is not a single process but rather a series of layered fusion events, uniquely different from the simple fusion of two epithelial surfaces as occurs in formation of the palate and neural tube. Copyright © 2016 International Society

  8. Complex epithelial remodeling underlie the fusion event in early fetal development of the human penile urethra

    Science.gov (United States)

    Sinclair, Adriane; Cao, Mei; Yue, Xuan; Cunha, Gerald; Baskin, Laurence

    2016-01-01

    We recently described a two-step process of urethral plate canalization and urethral fold fusion to form the human penile urethra. Canalization (“opening zipper”) opens the solid urethral plate into a groove, and fusion (“closing zipper”) closes the urethral groove to form the penile urethra. We hypothesize that failure of canalization and/or fusion during human urethral formation can lead to hypospadias. Herein, we use scanning electron microscopy (SEM) and analysis of transverse serial sections to better characterize development of the human fetal penile urethra as contrasted to the development of the human fetal clitoris. Eighteen 7-13 week human fetal external genitalia specimens were analyzed by SEM, and fifteen additional human fetal specimens were sectioned for histologic analysis. SEM images demonstrate canalization of the urethral/vestibular plate in the developing male and female external genitalia, respectively, followed by proximal to distal fusion of the urethral folds in males only. The fusion process during penile development occurs sequentially in multiple layers and through the interlacing of epidermal “cords”. Complex epithelial organization is also noted at the site of active canalization. The demarcation between the epidermis of the shaft and the glans becomes distinct during development, and the epithelial tag at the distal tip of the penile and clitoral glans regresses as development progresses. In summary, SEM analysis of human fetal specimens supports the two-zipper hypothesis of formation of the penile urethra. The opening zipper progresses from proximal to distal along the shaft of the penis and clitoris into the glans in identical fashion in both sexes. The closing zipper mechanism is active only in males and is not a single process but rather a series of layered fusion events, uniquely different from the simple fusion of two epithelial surfaces as occurs in formation of the palate and neural tube. PMID:27397682

  9. Sexually dimorphic adaptations in basal maternal stress physiology during pregnancy and implications for fetal development.

    Science.gov (United States)

    Giesbrecht, Gerald F; Campbell, Tavis; Letourneau, Nicole

    2015-06-01

    There is clear evidence of reciprocal exchange of information between the mother and fetus during pregnancy but the majority of research in this area has focussed on the fetus as a recipient of signals from the mother. Specifically, physiological signals produced by the maternal stress systems in response to the environment may carry valuable information about the state of the external world. Prenatal stress produces sex-specific adaptations within fetal physiology that have pervasive and long-lasting effects on development. Little is known, however, about the effects of sex-specific fetal signals on maternal adaptations to pregnancy. The current prospective study examined sexually dimorphic adaptations within maternal stress physiology, including the hypothalamic-adrenal-pituitary (HPA) axis and the autonomic nervous system (ANS) and associations with fetal growth. Using diurnal suites of saliva collected in early and late pregnancy, we demonstrate that basal cortisol and salivary alpha-amylase (sAA) differ by fetal sex. Women carrying female fetuses displayed greater autonomic arousal and flatter (but more elevated) diurnal cortisol patterns compared to women carrying males. Women with flatter daytime cortisol trajectories and more blunted sAA awakening responses also had infants with lower birth weight. These maternal adaptations are consistent with sexually dimorphic fetal developmental/evolutionary adaptation strategies that favor growth for males and conservation of resources for females. The findings provide new evidence to suggest that the fetus contributes to maternal HPA axis and ANS regulation during pregnancy and that these systems also contribute to the regulation of fetal growth. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. The Gini coefficient: a methodological pilot study to assess fetal brain development employing postmortem diffusion MRI

    Energy Technology Data Exchange (ETDEWEB)

    Viehweger, Adrian; Sorge, Ina; Hirsch, Wolfgang [University Hospital Leipzig, Department of Pediatric Radiology, Leipzig (Germany); Riffert, Till; Dhital, Bibek; Knoesche, Thomas R.; Anwander, Alfred [Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig (Germany); Stepan, Holger [University Leipzig, Department of Obstetrics, Leipzig (Germany)

    2014-10-15

    Diffusion-weighted imaging (DWI) is important in the assessment of fetal brain development. However, it is clinically challenging and time-consuming to prepare neuromorphological examinations to assess real brain age and to detect abnormalities. To demonstrate that the Gini coefficient can be a simple, intuitive parameter for modelling fetal brain development. Postmortem fetal specimens(n = 28) were evaluated by diffusion-weighted imaging (DWI) on a 3-T MRI scanner using 60 directions, 0.7-mm isotropic voxels and b-values of 0, 150, 1,600 s/mm{sup 2}. Constrained spherical deconvolution (CSD) was used as the local diffusion model. Fractional anisotropy (FA), apparent diffusion coefficient (ADC) and complexity (CX) maps were generated. CX was defined as a novel diffusion metric. On the basis of those three parameters, the Gini coefficient was calculated. Study of fetal brain development in postmortem specimens was feasible using DWI. The Gini coefficient could be calculated for the combination of the three diffusion parameters. This multidimensional Gini coefficient correlated well with age (Adjusted R{sup 2} = 0.59) between the ages of 17 and 26 gestational weeks. We propose a new method that uses an economics concept, the Gini coefficient, to describe the whole brain with one simple and intuitive measure, which can be used to assess the brain's developmental state. (orig.)

  11. Flt3 Ligand Regulates the Development of Innate Lymphoid Cells in Fetal and Adult Mice.

    Science.gov (United States)

    Baerenwaldt, Anne; von Burg, Nicole; Kreuzaler, Matthias; Sitte, Selina; Horvath, Edit; Peter, Annick; Voehringer, David; Rolink, Antonius G; Finke, Daniela

    2016-03-15

    Flt3 ligand (Flt3L) promotes survival of lymphoid progenitors in the bone marrow and differentiation of dendritic cells (DCs), but its role in regulating innate lymphoid cells (ILCs) during fetal and adult life is not understood. By using Flt3L knockout and transgenic mice, we demonstrate that Flt3L controls ILC numbers by regulating the pool of α4β7(-) and α4β7(+) lymphoid tissue inducer cell progenitors in the fetal liver and common lymphoid progenitors in the bone marrow. Deletion of flt3l severely reduced the number of fetal liver progenitors and lymphoid tissue inducer cells in the neonatal intestine, resulting in impaired development of Peyer's patches. In the adult intestine, NK cells and group 2 and 3 ILCs were severely reduced. This effect occurred independently of DCs as ILC numbers were normal in mice in which DCs were constitutively deleted. Finally, we could show that administration of Flt3L increased the number of NKp46(-) group 3 ILCs in wild-type and even in Il7(-/-) mice, which generally have reduced numbers of ILCs. Taken together, Flt3L significantly contributes to ILC and Peyer's patches development by targeting lymphoid progenitor cells during fetal and adult life.

  12. Placental vascular dysfunction, fetal and childhood growth, and cardiovascular development: the generation R study.

    Science.gov (United States)

    Gaillard, Romy; Steegers, Eric A P; Tiemeier, Henning; Hofman, Albert; Jaddoe, Vincent W V

    2013-11-12

    Suboptimal fetal nutrition may influence early growth and cardiovascular development. We examined whether umbilical and uterine artery resistance indices, as measures of feto-placental and utero-placental vascular function, respectively, are associated with fetal and childhood growth and cardiovascular development. This study was embedded in a population-based prospective cohort study among 6716 mothers and their children. Umbilical artery pulsatility index and uterine artery resistance index and fetal growth were measured in third trimester. Childhood growth was repeatedly assessed from birth to the age of 6 years. We measured body fat distribution, left ventricular mass, and blood pressure at the age of 6 years. Higher third trimester umbilical and uterine artery vascular resistance were associated with lower fetal length and weight growth in third trimester resulting in a smaller size at birth among boys and girls (P values growth became smaller from the age of 6 months onwards, but were still present at the age of 6 years. Higher third trimester umbilical artery vascular resistance, but not uterine artery vascular resistance, was associated with higher childhood body mass index, total fat mass, android/gynoid fat mass ratio, and systolic blood pressure, and with a lower left ventricular mass (P valuesgrowth rates and cardiovascular adaptations in childhood.

  13. Human cerebral organoids recapitulate gene expression programs of fetal neocortex development.

    Science.gov (United States)

    Camp, J Gray; Badsha, Farhath; Florio, Marta; Kanton, Sabina; Gerber, Tobias; Wilsch-Bräuninger, Michaela; Lewitus, Eric; Sykes, Alex; Hevers, Wulf; Lancaster, Madeline; Knoblich, Juergen A; Lachmann, Robert; Pääbo, Svante; Huttner, Wieland B; Treutlein, Barbara

    2015-12-22

    Cerebral organoids-3D cultures of human cerebral tissue derived from pluripotent stem cells-have emerged as models of human cortical development. However, the extent to which in vitro organoid systems recapitulate neural progenitor cell proliferation and neuronal differentiation programs observed in vivo remains unclear. Here we use single-cell RNA sequencing (scRNA-seq) to dissect and compare cell composition and progenitor-to-neuron lineage relationships in human cerebral organoids and fetal neocortex. Covariation network analysis using the fetal neocortex data reveals known and previously unidentified interactions among genes central to neural progenitor proliferation and neuronal differentiation. In the organoid, we detect diverse progenitors and differentiated cell types of neuronal and mesenchymal lineages and identify cells that derived from regions resembling the fetal neocortex. We find that these organoid cortical cells use gene expression programs remarkably similar to those of the fetal tissue to organize into cerebral cortex-like regions. Our comparison of in vivo and in vitro cortical single-cell transcriptomes illuminates the genetic features underlying human cortical development that can be studied in organoid cultures.

  14. Development of epithelia in the ectopic transplant of the fetal rat epiglottis.

    Science.gov (United States)

    Kulisić, Sandra Marinović; Jurić-Lekić, Gordana; Bulić-Jakus, Floriana; Radujković, Vedran; Parcetić, Ida; Vlahović, Maja; Katusić, Ana; Sincić, Nino; Serman, Ljiljana

    2008-01-01

    Embryonic in situ development is strictly regulated within the specific microenvironment of developing tissues. However, for regenerative medicine purposes (supplementation of damaged tissues/organs), transplantation to ectopic sites has been considered. To investigate developmental potential of fetal epiglottic epithelia at an ectopic site, fetal epiglottis was transplanted under the kidney capsule and its development compared to fetal and adult epiglottis. Seventeen-day-old Fischer rat epiglottides were microsurgically isolated under a dissecting microscope and transplanted under the kidney capsule of adult males. After 14 days, classic histology and immunohistochemical detection of the Proliferating Cell Nuclear Antigen (PCNA) were done in isolated and accordingly fixed transplants. The 17-day-old fetal epiglottis and adult epiglottis were processed in the same way. The 17-day-old fetal epiglottides were covered with immature epithelium expressing PCNA in almost all cells. Adult epiglottis was covered with two types of epithelia (stratified squamous epithelium and ciliated pseudostratified epithelium). In the stratified squamous epithelium PCNA was abundantly expressed in the basal cell layer and absent from more superficial and more differentiated cells. Transplants survived well during the experimental period. On their surface ciliated pseudostratified epithelium could be easily recognized, but squamous epithelium was almost absent. PCNA was expressed in basal cells of the ciliated pseudostratified epithelium and was absent from the more differentiated superficial cells. It seems that at this ectopic site further differentiation of the epiglottic epithelia can proceed but differentiation of squamous epithelium seems not to be favored. It seems that this ectopic site is optimal for further differentiation of the epiglottic epithelium towards ciliated pseudostratified epithelium.

  15. Intact fetal ovarian cord formation promotes mouse oocyte survival and development

    Directory of Open Access Journals (Sweden)

    Pera Renee

    2010-01-01

    Full Text Available Abstract Background Female reproductive potential, or the ability to propagate life, is limited in mammals with the majority of oocytes lost before birth. In mice, surviving perinatal oocytes are enclosed in ovarian follicles for subsequent oocyte development and function in the adult. Before birth, fetal germ cells of both sexes develop in clusters, or germline cysts, in the undifferentiated gonad. Upon sex determination of the fetal gonad, germ cell cysts become organized into testicular or ovarian cord-like structures and begin to interact with gonadal somatic cells. Although germline cysts and testicular cords are required for spermatogenesis, the role of cyst and ovarian cord formation in mammalian oocyte development and female fertility has not been determined. Results Here, we examine whether intact fetal ovarian germ and somatic cell cord structures are required for oocyte development using mouse gonad re-aggregation and transplantation to disrupt gonadal organization. We observed that germ cells from disrupted female gonad prior to embryonic day e13.5 completed prophase I of meiosis but did not survive following transplantation. Furthermore, re-aggregated ovaries from e13.5 to e15.5 developed with a reduced number of oocytes. Oocyte loss occurred before follicle formation and was associated with an absence of ovarian cord structure and ovary disorganization. However, disrupted ovaries from e16.5 or later were resistant to the re-aggregation impairment and supported robust oocyte survival and development in follicles. Conclusions Thus, we demonstrate a critical window of oocyte development from e13.5 to e16.5 in the intact fetal mouse ovary, corresponding to the establishment of ovarian cord structure, which promotes oocyte interaction with neighboring ovarian somatic granulosa cells before birth and imparts oocytes with competence to survive and develop in follicles. Because germline cyst and ovarian cord structures are conserved in the

  16. Impact of maternal undernutrition during the periconceptional period, fetal number, and fetal sex on the development of the hypothalamo-pituitary adrenal axis in sheep during late gestation.

    Science.gov (United States)

    Edwards, L J; McMillen, I Caroline

    2002-05-01

    Evidence from epidemiologic, clinical, and experimental studies has shown that a suboptimal intrauterine environment during early pregnancy can alter fetal growth and gestation length and is associated with an increased prevalence of adult hypertension and cardiovascular disease. It has been postulated that maternal nutrient restriction may act to reprogram the development of the pituitary-adrenal axis, resulting in excess glucocorticoid exposure and adverse health outcomes in later life. It is unknown, however, whether maternal nutrient restriction during the periconceptional period alters the development of the fetal pituitary-adrenal axis or whether the effects of periconceptional undernutrition can be reversed by the provision of an adequate level of maternal nutrition throughout the remainder of pregnancy. We have investigated the effect of restricted periconceptional nutrition (70% of control feed allowance) from 60 days before until 7 days after mating and the effect of restricted gestational nutrition from Day 8 to 147 of gestation on the development of the fetal hypothalamo-pituitary adrenal (HPA) axis in the sheep. In these studies, we have also investigated the effects of fetal number and sex on the pituitary-adrenal responses to periconceptional and gestational undernutrition. In ewes maintained on a control diet throughout the periconceptional and gestational periods, fetal plasma ACTH concentrations were higher and the prepartum surge in cortisol occurred earlier in singletons compared with twins. Plasma ACTH concentrations were also significantly higher in male compared with female singletons, and in twin fetuses, the prepartum surge in cortisol concentrations occurred earlier in males than in females. Periconceptional undernutrition resulted in higher fetal plasma concentrations of ACTH between 110 and 145 days of gestation and a significantly greater cortisol response to a bolus dose of corticotropin-releasing hormone in twin, but not singleton

  17. Effect of IFN-γ and dexamethasone on TGF-β1-induced human fetal lung fibroblast-myofibroblast differentiation

    Institute of Scientific and Technical Information of China (English)

    Li GU; Yuan-jue ZHU; Zi-jian GUO; Xing-xiang XU; Wen-bing XU

    2004-01-01

    AIM: To study whether Smads signaling pathway was involved in human fetal lung fibroblast-myofibroblast differentiation induced by transforming growth factor (TGF)-β1 and the role of interferon (IFN)-γ, dexamethasone (DEX)in the fibroblast-myofibroblast differentiation. METHODS: α-Smooth muscle actin (α-SMA), Smad2/3, and Smad7protein were assessed by Western blot. Collagen protein was analyzed by measuring hydroxyproline. α-SMA and collagen Ⅲ mRNA were assessed by RT-PCR. Myofibroblasts morphology and Smad2/3 nuclear translocation were assessed by immunohistochemistry. The overexpression of Smad7, a negative mediator of Smads signaling pathway, was acquired by transfection of Smad7 vector. RESULTS: During fibroblast-myofibroblast differentiation induced by TGF-β1, IFN-γ 200 μg/L markedly blocked TGF-β1-induced α-SMA protein expression (P<0.01),collagen protein (P<0.01) and mRNA (P<0.05) expression, and myofibroblasts morphological transformation, but DEX 10 μmol/L augmented TGF-β1-induced α-SMA expression (P<0.01). For myofibroblasts, both IFN-γ 200 μg/L and DEX 10 μmol/L did not inhibit α-SMA expression (P>0.05) and collagen protein (P>0.05) and mRNA expression (P>0.05) and did not change myofibroblasts morphology. Transient transfection of Smad7 vector resulted in significant inhibition of TGF-β1-induced α-SMA expression (P<0.01). IFN-γ 200 μg/L did not block TGF-β1-stimulated Smad2/3 phosphorylation and their nuclear translocation. CONCLUSION: TGF-β1 induced fibroblastmyofibroblast differentiation in a Smad proteins-dependent manner. IFN-γ could block this process but it was not mediated by interrupting smad2/3 phosphorylation and their nuclear translocation and DEX played a synergism with TGF-β1. Differentiated myofibroblasts, however, were resistant to both IFN-γ and DEX.

  18. IGF2 DNA methylation is a modulator of newborn's fetal growth and development.

    Science.gov (United States)

    St-Pierre, Julie; Hivert, Marie-France; Perron, Patrice; Poirier, Paul; Guay, Simon-Pierre; Brisson, Diane; Bouchard, Luigi

    2012-10-01

    The insulin-like growth factor 2 (IGF2) gene, located within a cluster of imprinted genes on chromosome 11p15, encodes a fetal and placental growth factor affecting birth weight. DNA methylation variability at the IGF2 gene locus has been previously reported but its consequences on fetal growth and development are still mostly unknown in normal pediatric population. We collected one hundred placenta biopsies from 50 women with corresponding maternal and cord blood samples and measured anthropometric indices, blood pressure and metabolic phenotypes using standardized procedures. IGF2/H19 DNA methylation and IGF2 circulating levels were assessed using sodium bisulfite pyrosequencing and ELISA, respectively. Placental IGF2 (DMR0 and DMR2) DNA methylation levels were correlated with newborn's fetal growth indices, such as weight, and with maternal IGF2 circulating concentration at the third trimester of pregnancy, whereas H19 (DMR) DNA methylation levels were correlated with IGF2 levels in cord blood. The maternal genotype of a known IGF2/H19 polymorphism (rs2107425) was associated with birth weight. Taken together, we showed that IGF2/H19 epigenotype and genotypes independently account for 31% of the newborn's weight variance. No association was observed with maternal diabetic status, glucose concentrations or prenatal maternal body mass index. This is the first study showing that DNA methylation at the IGF2/H19 genes locus may act as a modulator of IGF2 newborn's fetal growth and development within normal range. IGF2/H19 DNA methylation could represent a cornerstone in linking birth weight and fetal metabolic programming of late onset obesity.

  19. Allometric growth in the extant coelacanth lung during ontogenetic development.

    Science.gov (United States)

    Cupello, Camila; Brito, Paulo M; Herbin, Marc; Meunier, François J; Janvier, Philippe; Dutel, Hugo; Clément, Gaël

    2015-09-15

    Coelacanths are lobe-finned fishes known from the Devonian to Recent that were long considered extinct, until the discovery of two living species in deep marine waters of the Mozambique Channel and Sulawesi. Despite extensive studies, the pulmonary system of extant coelacanths has not been fully investigated. Here we confirm the presence of a lung and discuss its allometric growth in Latimeria chalumnae, based on a unique ontogenetic series. Our results demonstrate the presence of a potentially functional, well-developed lung in the earliest known coelacanth embryo, and its arrested growth at later ontogenetic stages, when the lung is clearly vestigial. The parallel development of a fatty organ for buoyancy control suggests a unique adaptation to deep-water environments. Furthermore, we provide the first evidence for the presence of small, hard, flexible plates around the lung in L. chalumnae, and consider them homologous to the plates of the 'calcified lung' of fossil coelacanths.

  20. Lung abscess mimicking lung cancer developed around staples in a patient with permanent tracheostoma.

    Science.gov (United States)

    Watanabe, Yui; Aoki, Masaya; Suzuki, Soichi; Umehara, Tadashi; Harada, Aya; Wakida, Kazuhiro; Nagata, Toshiyuki; Kariatsumari, Kota; Nakamura, Yoshihiro; Sato, Masami

    2015-11-01

    A 68-year-old male with a tracheostoma due to hypopharyngeal cancer was admitted because his chest computed tomography (CT) showed a small nodule in the right middle lobe. Following a partial resection of the right middle lobe, histopathological diagnosis of the resected sample was that of organizing pneumonia. Eleven months later, chest CT showed a mass with pleural indentation and spiculation in the right middle lobe. 18-Fluorodeoxyglucose-positron emission tomography showed significant accumulation in the middle lobe tumor mass shadow. The abnormal chest shadow that had developed around surgical staples suggested inadequate resection and tumor recurrence. As the abnormal radiological shadow was enlarging, middle lobectomy was carried out. Histological examination revealed that the tumor was a lung abscess without malignant features. This is a unique case of lung abscess mimicking lung cancer which developed around staples used during partial resection of the lung.

  1. Functions of Maternally-Derived Taurine in Fetal and Neonatal Brain Development.

    Science.gov (United States)

    Tochitani, Shiro

    2017-01-01

    Taurine (2-aminoethanesulfonic acid) is a sulfur-containing organic acid, which has various physiological functions, including membrane stabilization, cell-volume regulation, mitochondrial protein translocation, anti-oxidative activity, neuroprotection against neurotoxicity and modulation of intracellular calcium levels. Taurine also activates GABAA receptors and glycine receptors. Mammalian fetuses and infants are dependent on taurine delivered from their mothers via either the placenta or their mother's milk. Taurine is a molecule that links mother-fetus or mother-infant bonding.This review describes the functions of taurine and the mechanisms of action of taurine in fetal and brain development. Taurine is involved in regulating the proliferation of neural progenitors, migration of newly-generated neurons, and the synapse formation of neurons after migration during fetal and neonatal development. In this review, we also discuss the environmental factors that might influence the functional roles of taurine in neural development.

  2. Alveolar flows of the developing lungs:from embryonic to early childhood airways

    Science.gov (United States)

    Tenenbaum-Katan, Janna; Hofemeier, Philipp; Fishler, Rami; Rothen-Rutishauser, Barbara; Sznitman, Josue

    2014-11-01

    At the onset of life in utero the respiratory system is simply a liquid-filled duct. With our first breath, alveoli are filled with air and become a significant port of entry for airborne particles. As such, alveolar lining is nearly fully functional at birth, though lung development continues during childhood as structural changes increase alveolar surface area to optimize ventilation. We hypothesize that such fluid dynamical changes potentially affect two phenomena occurring within alveoli: (i) flow patterns in airspaces at distinct stages of both in- and ex-utero life and (ii) fate of inhaled particles ex-utero. To investigate these phenomena, we combine experimental and numerical approaches where (i) microfluidic in vitro devices mimic liquid flows across the epithelium of fetal airspaces, and (ii) computational simulations are employed to examine particle transport and deposition in the deep alveolated regions of infants' lungs. Our approaches capture anatomically-inspired geometries based on morphometrical data, as well as physiological flows, including the convective-diffusive nature of submicron particle transport in alveolar regions.Overall, we investigate respiratory flows in alveolar regions of developing lungs, from early embryonic stages to late childhood

  3. Efeito da icterícia obstrutiva na fertilidade, morfologia ovariana e desenvolvimento fetal em ratas Effect of jaundice on fertility, ovarian morphology and fetal development in rats

    Directory of Open Access Journals (Sweden)

    Vivian Resende

    2008-09-01

    Full Text Available Avaliou-se o efeito da icterícia obstrutiva na capacidade reprodutiva, morfologia ovariana e desenvolvimento fetal em ratas, utilizando 53 ratas sexualmente maduras, distribuídas em dois grupos: grupo 1 (n = 28 - ligadura do ducto biliopancreático e grupo 2 (n = 25 - controle. Pode-se concluir que, em presença de hiperbilirrubinemia, a fertilização é viável, a capacidade reprodutiva é muito reduzida, os ciclos estrais tornam-se irregulares, o epitélio vaginal permanece cornificado, os corpos lúteos ovarianos regridem, os corpos lúteos gravídicos não são alterados, aumentando progressivamente durante a prenhez, e o desenvolvimento fetal é gravemente alterado.The effect of jaundice on the reproductive capacity, ovarian morphology and fetal development in rats was assessed in 53 sexually mature rats divided into two groups: group 1 (n = 28 - submitted to ligature of the biliopancreatic duct and group 2 (n = 25 - control - submitted only to sham operation. In jaundice rats fertilization is viable, the reproductive capacity is intensive reduced, the estrus cycles becomes irregular, the corpi lutea is presented in regression, the gravidic lutea is not modified increasing gradually during the pregnancy and the fetal development is seriously impaired.

  4. Transcriptional regulation of lung development: emergence of specificity

    Directory of Open Access Journals (Sweden)

    Minoo Parviz

    2000-09-01

    Full Text Available Abstract The lung is the product of a set of complex developmental interactions between two distinct tissues, the endodermally derived epithelium and the mesoderm. Each tissue contributes to lung development by fine-tuning the spatial and temporal pattern of gene expression for a distinct array of signaling molecules, transcriptional molecules and molecules related to the extracellular matrix. Morphoregulatory transcriptional factors such as NKX2.1 have the crucial role of connecting the cell–cell crosstalk to the activation or repression of gene expression through which processes such as cellular proliferation, migration, differentiation and apoptosis can be controlled. Although none of the factors participating in lung development are exclusively lung-specific, their unique combinations and interactions constitute the basis for emergence of lung structural and functional specificities. An understanding of the individual molecules and their unique interactions in the context of lung development is necessary for the construction of a morphogenetic map for this vital organ as well as for the development of rational and innovative approaches to congenital and induced lung disease.

  5. Ventilation-induced Alterations in Lung Development

    NARCIS (Netherlands)

    A.A. Kroon (André)

    2011-01-01

    textabstractMechanical ventilation is a lifesaving treatment in critically ill neonates. However, mechanical ventilation is also one of the most important risk factors (Table 1) of Bronchopulmonary dysplasia (BPD), the most common chronic lung disease in infancy with long-term pulmonary and neurolog

  6. Metabolic gene profile in early human fetal heart development

    National Research Council Canada - National Science Library

    Iruretagoyena, J I; Davis, W; Bird, C; Olsen, J; Radue, R; Teo Broman, A; Kendziorski, C; Splinter BonDurant, S; Golos, T; Bird, I; Shah, D

    2014-01-01

    .... In order to describe normal cardiac development during late first and early second trimester in human fetuses this study used microarray and pathways analysis and created a corresponding 'normal' database...

  7. Graphic Evolution Witness the Development of Lung Cancer Translational Research

    Directory of Open Access Journals (Sweden)

    Chao ZHANG

    2016-06-01

    Full Text Available Lung cancer treatment has altered from conventional chemotherapy to targeted treatment, which now has been turned to the immunotherapy. Translational research has played an irreplaceable role during this progression which graphic evolution has witnessed. The evolution has gone through forest plot, KM-curve, waterfall plot, spider plot and timeline-area, showing us the refining concept and gradual process of lung cancer treatment undergoing from community towards individual. Even though the latest immunotherapy is getting increasingly hot, the result isn’t quite expected. Meanwhile, the limitations of conventional treatment still exist which require further research. This article will primarily illustrate the development of translational research of lung cancer via the aspect of curve evolution and analysis some abortive clinical trials in lung cancer surgery for inspiring the next graphic style and lung cancer treatment.

  8. Prenatal MR imaging of congenital diaphragmatic hernias: association of MR fetal lung volume with the need for postnatal prosthetic patch repair

    Energy Technology Data Exchange (ETDEWEB)

    Hagelstein, Claudia; Weidner, Meike; Schoenberg, Stefan O.; Buesing, Karen A.; Neff, K.W. [University of Heidelberg, Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Mannheim (Germany); Zahn, Katrin [University of Heidelberg, Department of Pediatric Surgery, University Medical Center Mannheim, Mannheim (Germany); Weiss, Christel [University of Heidelberg, Department of Medical Statistics and Biomathematics, University Medical Center Mannheim, Mannheim (Germany); Schaible, Thomas [University of Heidelberg, Department of Pediatrics, University Medical Center Mannheim, Mannheim (Germany)

    2015-01-15

    To assess whether the need for postnatal prosthetic patch repair of the diaphragmatic defect in neonates with a congenital diaphragmatic hernia (CDH) is associated with the antenatal measured observed-to-expected magnetic resonance fetal lung volume (o/e MR-FLV). The o/e MR-FLV was calculated in 247 fetuses with isolated CDH. Logistic regression analysis was used to assess the prognostic value of the individual o/e MR-FLV for association with the need for postnatal patch repair. Seventy-seven percent (77 %) of patients with a CDH (190/247) required prosthetic patch repair and the defect was closed primarily in 23 % (57/247). Patients requiring a patch had a significantly lower o/e MR-FLV (27.7 ± 10.2 %) than patients with primary repair (40.8 ± 13.8 %, p < 0.001, AUC = 0.786). With an o/e MR-FLV of 20 %, 92 % of the patients required patch repair, compared to only 24 % with an o/e MR-FLV of 60 %. The need for a prosthetic patch was further influenced by the fetal liver position (herniation/no herniation) as determined by magnetic resonance imaging (MRI; p < 0.001). Fetal liver position, in addition to the o/e MR-FLV, improves prognostic accuracy (AUC = 0.827). Logistic regression analysis based on the o/e MR-FLV is useful for prenatal estimation of the prosthetic patch requirement in patients with a CDH. In addition to the o/e MR-FLV, the position of the liver as determined by fetal MRI helps improve prognostic accuracy. (orig.)

  9. First trimester alcohol exposure alters placental perfusion and fetal oxygen availability affecting fetal growth and development in a non-human primate model.

    Science.gov (United States)

    Lo, Jamie O; Schabel, Matthias C; Roberts, Victoria H J; Wang, Xiaojie; Lewandowski, Katherine S; Grant, Kathleen A; Frias, Antonio E; Kroenke, Christopher D

    2017-03-01

    Prenatal alcohol exposure leads to impaired fetal growth, brain development, and stillbirth. Placental impairment likely contributes to these adverse outcomes, but the mechanisms and specific vasoactive effects of alcohol that links altered placental function to impaired fetal development remain areas of active research. Recently, we developed magnetic resonance imaging techniques in nonhuman primates to characterize placental blood oxygenation through measurements of T2* and perfusion using dynamic contrast-enhanced magnetic resonance imaging. The objective of this study was to evaluate the effects of first-trimester alcohol exposure on macaque placental function and to characterize fetal brain development in vivo. Timed-pregnant Rhesus macaques (n=12) were divided into 2 groups: control (n=6) and ethanol exposed (n=6). Animals were trained to self-administer orally either 1.5 g/kg/d of a 4% ethanol solution (equivalent to 6 drinks/d) or an isocaloric control fluid from preconception until gestational day 60 (term is G168). All animals underwent Doppler ultrasound scanning followed by magnetic resonance imaging that consisted of T2* and dynamic contrast-enhanced measurements. Doppler ultrasound scanning was used to measure uterine artery and umbilical vein velocimetry and diameter to calculate uterine artery volume blood flow and placental volume blood flow. After noninvasive imaging, animals underwent cesarean delivery for placenta collection and fetal necropsy at gestational day 110 (n=6) or 135 (n=6). Fetal weight and biparietal diameter were significantly smaller in ethanol-exposed animals compared with control animals at gestational day 110. By Doppler ultrasound scanning, placental volume blood flow was significantly lower (P=.04) at gestational day 110 in ethanol-exposed vs control animals. A significant reduction in placental blood flow was evident by dynamic contrast-enhanced magnetic resonance imaging. As we demonstrated recently, T2* values vary

  10. Stimulation of 11β-HSD1 expression by IL-1β via a C/EBP binding site in human fetal lung fibroblasts.

    Science.gov (United States)

    Yang, Zhen; Zhu, Xiaoou; Guo, Chunming; Sun, Kang

    2009-12-01

    Proinflammatory cytokines, just like glucocorticoids (GCs), have been reported to upregulate 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) expression in many cell types. This concerted regulation of 11β-HSD1 by interleukin-1β (IL-1β) and GCs is in marked contrast to their antagonistic effects on inflammation. Further, the molecular mechanisms underlying the induction of 11β-HSD1 by IL-1β are not very well understood. In this study, we demonstrated that IL-1β dramatically stimulated 11β-HSD1 expression and enzyme activity as well as promoter activity including the -64 bp fragment upstream to the transcription start site in human fetal lung fibroblasts (HFL-1). Nucleotide mutations of the proximal CCAAT box within this region abolished the induction of 11β-HSD1 promoter activity by IL-1β. Western blotting analysis demonstrated that IL-1β induced the expression of C/EBPβ dramatically while C/EBPα was barely detectable in HFL-1 cells. Global inhibition of CCAAT/enhancer-binding proteins (C/EBPs) with transfection of C/EBP-specific dominant-negative expression plasmid (CMV500-A-C/EBP) significantly attenuated the induction of 11β-HSD1 by IL-1β, whereas over-expression of C/EBPβ enhanced the expression of 11β-HSD1. Chromatin immunoprecipitation assay revealed the recruitment of C/EBPβ to the promoter region containing the C/EBP binding site. In conclusion, IL-1β induces the expression of 11β-HSD1 mRNA in the fetal lung tissue through mechanisms that involve C/EBPβ binding to the promoter. This impact of IL-1β on the expression of 11β-HSD1 in human fetal lung cells may explain the alternate mechanism for the lung maturation that appears to occur when there is a risk of premature delivery of the fetus due to the presence of infection.

  11. Gestational nanomaterial exposures: microvascular implications during pregnancy, fetal development and adulthood.

    Science.gov (United States)

    Stapleton, P A

    2016-04-15

    Air pollution particulate matter and engineered nanomaterials are encompassed in the broad definition of xenobiotic particles. While the effects of perinatal air pollution exposure have been investigated, elucidation of outcomes associated with nanomaterial exposure, the focus of this review, is still in its infancy. As the potential uses of nanomaterials, and therefore exposures, increase exponentially so does the need for thorough evaluation. Up to this point, the majority of research in the field of cardiovascular nanotoxicology has focused on the coronary and vascular reactions to pulmonary exposures in young adult, healthy, male models; however, as intentional and unintentional contacts persist, the non-pulmonary risks to under-represented populations become a critical concern. Development of the maternal-fetal circulation during successful mammalian gestation is one of the most unusual complex, dynamic, and acutely demanding physiological systems. Fetal development in a hostile gestational environment can lead to systemic alterations, which may encourage adult disease. Therefore, the purpose of this review is to highlight the few knowns associated with gestational engineered nanomaterial exposure segmented by physiological periods of development or systemic targets: preconception and maternal, gestational, fetal and progeny (Abstract figure). Overall, the limited studies currently available provide compelling evidence of maternal, fetal and offspring dysfunctions after engineered nanomaterial exposure. Understanding the mechanisms associated with these multigenerational effects may allow pregnant women to safely reap the benefits of nanotechnology-enabled products and assist in the implementation of exposure controls to protect the mother and fetus allowing for development of safety by design for engineered nanomaterials. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  12. 空气污染对胎儿生长发育的影响及作用机制%Impact of air pollution on fetal development

    Institute of Scientific and Technical Information of China (English)

    郑林媚; 洪新如; 孙庆华

    2011-01-01

    Numerous researches on the health effects of air pollution have been reported during the last decade. Epidemiological and experimental studies have shown that prenatal exposure to air pollutants is associated with adverse birth outcome including low birth weight ( LBW), preterm birth ( PTB ), intrauterine growth restriction ( IUGR), congenital defects, prolonged fetal lung growth,stillbirth, fetal death and neonatal death. This article retrospectively overviews the influence of air pollution on the fetal development and its mechanisms.%近十年来,已经有了越来越多关于空气污染与胚胎发育影响的研究报告.流行病学观察和实验研究等均显示,产前暴露于空气污染与低出生体重(LBW)、早产(PrB)、胎儿宫内生长受限(IUGR)、先天性缺陷、胎肺发育延迟、死胎、死产和新生儿死亡等不良妊娠结局有关.本文回顾空气污染物胎儿生长发育的影响及其作用机制的研究进展.

  13. Programmed cell death in developing human fetal CNS

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The spatial and temporal distributions of programmed cell death (PCD) in developing central nervous system (CNS) of human fetuses ranging from 12 to 39 weeks of gestation were investigated using techniques of flow cytometry and terminal transferase-mediated nick end labeling (TUNEL). The results showed that PCD did occur in every representative brain region of all fetuses examined in different stages. It was found that there were two peaks of PCD appearing at the 12th and 39th weeks respectively, which suggested that the first peak of apoptosis may be involved in the selective elimination of neurons overproduced during the early development and the second may play an important role in establishing the correct neuronal circuitry.

  14. Air pollution during pregnancy and lung development in the child.

    Science.gov (United States)

    Korten, Insa; Ramsey, Kathryn; Latzin, Philipp

    2017-01-01

    Air pollution exposure has increased extensively in recent years and there is considerable evidence that exposure to particulate matter can lead to adverse respiratory outcomes. The health impacts of exposure to air pollution during the prenatal period is especially concerning as it can impair organogenesis and organ development, which can lead to long-term complications. Exposure to air pollution during pregnancy affects respiratory health in different ways. Lung development might be impaired by air pollution indirectly by causing lower birth weight, premature birth or disturbed development of the immune system. Exposure to air pollution during pregnancy has also been linked to decreased lung function in infancy and childhood, increased respiratory symptoms, and the development of childhood asthma. In addition, impaired lung development contributes to infant mortality. The mechanisms of how prenatal air pollution affects the lungs are not fully understood, but likely involve interplay of environmental and epigenetic effects. The current epidemiological evidence on the effect of air pollution during pregnancy on lung function and children's respiratory health is summarized in this review. While evidence for the adverse effects of prenatal air pollution on lung development and health continue to mount, rigorous actions must be taken to reduce air pollution exposure and thus long-term respiratory morbidity and mortality.

  15. Forebrain development in fetal MRI: evaluation of anatomical landmarks before gestational week 27.

    Science.gov (United States)

    Schmook, Maria T; Brugger, Peter C; Weber, Michael; Kasprian, Gregor; Nemec, Stefan; Krampl-Bettelheim, Elisabeth; Prayer, Daniela

    2010-06-01

    Forebrain malformations include some of the most severe developmental anomalies and require early diagnosis. The proof of normal or abnormal prosencephalic development may have an influence on further management in the event of a suspected fetal malformation. The purpose of this retrospective study was to evaluate the detectability of anatomical landmarks of forebrain development using in vivo fetal magnetic resonance imaging (MRI) before gestational week (gw) 27. MRI studies of 83 singleton fetuses (gw 16-26, average +/- sd: gw 22 +/- 2) performed at 1.5 Tesla were assessed. T2-weighted (w) fast spin echo, T1w gradient-echo and diffusion-weighted sequences were screened for the detectability of anatomical landmarks as listed below. The interhemispheric fissure, ocular bulbs, corpus callosum, infundibulum, chiasm, septum pellucidum (SP), profile, and palate were detectable in 95%, 95%, 89%, 87%, 82%, 81%, 78%, 78% of cases. Olfactory tracts were more easily delineated than bulbs and sulci (37% versus 18% and 8%), with significantly higher detection rates in the coronal plane. The pituitary gland could be detected on T1w images in 60% with an increasing diameter with gestational age (p = 0.041). The delineation of olfactory tracts (coronal plane), chiasm, SP and pituitary gland were significantly increased after week 21 (p < 0.05). Pathologies were found in 28% of cases. This study provides detection rates for anatomical landmarks of forebrain development with fetal MRI before gw 27. Several anatomical structures are readily detectable with routine fetal MRI sequences; thus, if these landmarks are not delineable, it should raise the suspicion of a pathology. Recommendations regarding favorable sequences/planes are provided.

  16. Forebrain development in fetal MRI: evaluation of anatomical landmarks before gestational week 27

    Energy Technology Data Exchange (ETDEWEB)

    Schmook, Maria T.; Weber, Michael; Kasprian, Gregor; Nemec, Stefan; Prayer, Daniela [Medical University of Vienna, Department of Radiology/Division of Neuro- and Musculoskeletal Radiology, Vienna (Austria); Brugger, Peter C. [Medical University of Vienna, Integrative Morphology Group, Center for Anatomy and Cell Biology, Vienna (Austria); Krampl-Bettelheim, Elisabeth [Department of Obstetrics and Gynecology / Division of Obstetrics and Feto-maternal Medicine, Vienna (Austria)

    2010-06-15

    Forebrain malformations include some of the most severe developmental anomalies and require early diagnosis. The proof of normal or abnormal prosencephalic development may have an influence on further management in the event of a suspected fetal malformation. The purpose of this retrospective study was to evaluate the detectability of anatomical landmarks of forebrain development using in vivo fetal magnetic resonance imaging (MRI) before gestational week (gw) 27. MRI studies of 83 singleton fetuses (gw 16-26, average {+-}sd: gw 22 {+-} 2) performed at 1.5 Tesla were assessed. T2-weighted (w) fast spin echo, T1w gradient-echo and diffusion-weighted sequences were screened for the detectability of anatomical landmarks as listed below. The interhemispheric fissure, ocular bulbs, corpus callosum, infundibulum, chiasm, septum pellucidum (SP), profile, and palate were detectable in 95%, 95%, 89%, 87%, 82%, 81%, 78%, 78% of cases. Olfactory tracts were more easily delineated than bulbs and sulci (37% versus 18% and 8%), with significantly higher detection rates in the coronal plane. The pituitary gland could be detected on T1w images in 60% with an increasing diameter with gestational age (p=0.041). The delineation of olfactory tracts (coronal plane), chiasm, SP and pituitary gland were significantly increased after week 21 (p<0.05). Pathologies were found in 28% of cases. This study provides detection rates for anatomical landmarks of forebrain development with fetal MRI before gw 27. Several anatomical structures are readily detectable with routine fetal MRI sequences; thus, if these landmarks are not delineable, it should raise the suspicion of a pathology. Recommendations regarding favorable sequences/planes are provided. (orig.)

  17. Fibronectin distribution during the development of fetal rat skin

    DEFF Research Database (Denmark)

    Gibson, W T; Couchman, J R; Weaver, A C

    1983-01-01

    revealed fibronectin on the surface of many of these cells and in association with the surrounding fine collagen fibrils. At the dermal-epidermal junction, both follicular and interfollicular, fibronectin was localized mainly in the plasma membrane and lamina lucida regions of the basement membrane......, and there was also staining associated with the underlying fine collagen fibrils. These observations are further evidence for the proposed role of fibronectin as a mediator of the cell-matrix interactions which are of importance for tissue development and maintenance....

  18. Contagem de corpos lamelares versus teste de Clements na avaliação da maturidade pulmonar fetal em gestantes diabéticas Lamellar body count versus the shake test in the assessment of fetal lung maturity in diabetics

    Directory of Open Access Journals (Sweden)

    Guilherme Loureiro Fernandes

    2006-08-01

    Full Text Available OBJETIVOS: analisar a contagem dos corpos lamelares em comparação com o teste de Clements na avaliação da maturidade pulmonar fetal em gestantes diabéticas. MÉTODOS: estudo prospectivo envolvendo 62 gestantes submetidas a amniocentese entre a 26ª e a 39ª semana. O líquido amniótico foi imediatamente submetido ao teste de Clements e à contagem de corpos lamelares. Os partos ocorreram até três dias após a amniocentese. A ocorrência de síndrome de angústia respiratória, indicativa de imaturidade pulmonar, foi confrontada com os resultados de imaturidade da amniocentese (ausência de anel completo no 3º tubo e menos de 50.000 corpos lamelares. O teste do chi2 foi utilizado para comparar o desempenho dos dois métodos e pPURPOSE: to assess the performance of lamellar body count compared to the shake (Clements test in the prediction of fetal lung maturity in diabetics. METHODS: prospective study of 62 patients who underwent amniocentesis between the 26th and 39th week of pregnancy. Immediately after collection, the amniotic fluid sample was submitted to the shake test and lamellar body count. Deliveries occurred within three days of amniocentesis. Immature test results (absence of a complete bubble ring in the third tube for the shake test and less than 50,000 lamellar bodies were confronted with the occurrence of pulmonary immaturity in the neonate (respiratory distress syndrome. The performance of both tests was compared using the chi2 test and p<0.05 was considered to be significant. RESULTS: seven infants had respiratory distress syndrome (11.3%. The lamellar body count and shake test were similar regarding sensitivity (100 vs 71.4%, respectively and negative predictive value (100 vs 93.5%. Lamellar body count was superior as regards specificity (87.3 vs 52.7%, p=0.0001, positive predictive value (50 vs 16.1%, p=0.017, and accuracy (88.7 vs 54.8%, p<0.001. CONCLUSIONS: lamellar body count is a simple and accurate method of

  19. Sonic hedgehog signaling in the lung. From development to disease.

    Science.gov (United States)

    Kugler, Matthias C; Joyner, Alexandra L; Loomis, Cynthia A; Munger, John S

    2015-01-01

    Over the past two decades, the secreted protein sonic hedgehog (SHH) has emerged as a critical morphogen during embryonic lung development, regulating the interaction between epithelial and mesenchymal cell populations in the airway and alveolar compartments. There is increasing evidence that the SHH pathway is active in adult lung diseases such as pulmonary fibrosis, asthma, chronic obstructive pulmonary disease, and lung cancer, which raises two questions: (1) What role does SHH signaling play in these diseases? and (2) Is it a primary driver of the disease or a response (perhaps beneficial) to the primary disturbance? In this review we aim to fill the gap between the well-studied period of embryonic lung development and the adult diseased lung by reviewing the hedgehog (HH) pathway during the postnatal period and in adult uninjured and injured lungs. We elucidate the similarities and differences in the epithelial-mesenchymal interplay during the fibrosis response to injury in lung compared with other organs and present a critical appraisal of tools and agents available to evaluate HH signaling.

  20. A change in the number of CCSP(pos)/SPC(pos) cells in mouse lung during development, growth, and repair.

    Science.gov (United States)

    Sun, Ruowen; Zhou, Qiliang; Ye, Xulu; Takahata, Takenori; Ishiguro, Atsushi; Kijima, Hiroshi; Nukiwa, Toshihiro; Saijo, Yasuo

    2013-12-01

    Putative resident stem/progenitor cells have been identified in the bronchoalveolar duct junction (BADJ) of the murine lung. However, the contribution of stem cells expressing both Clara cell secretory protein (CCSP) and pro-surfactant protein C (SP-C) to the repair and maintenance of normal homeostasis is still unclear. In this study, we identified and then quantified CD45(neg)/CCSP(pos)/SP-C(pos) cell numbers in normal and lung-injured mice. Normal lung tissues of fetal, newborn, and adult mice were used to evaluate lung progenitor cells during development and growth. Mice treated with naphthalene were used for the bronchiolar epithelium injury model, and mice treated with bleomycin were used for the alveolar epithelium injury model. These lung tissues were stained with CD45, CCSP, and SP-C antibodies by immunofluorescence. The number of lung progenitor cells was counted as CD45(neg)/CCSP(pos)/SP-C(pos) cells by flow cytometry. CCSP(pos)/SP-C(pos) epithelial cells in the BADJ were identified from E18 to 7 months after birth. The percentage of CD45(neg)/CCSP(pos)/SP-C(pos) cells was relatively stable to 7 months (between 0.3±0.04% and 1.28±0.11%). When lungs were treated with naphthalene, the proliferation of CCSP(pos)/SP-C(pos) cells was observed as patches of double-positive cells and preceded the recovery of bronchioles. In contrast, when lungs were treated with bleomycin, the proliferation of CCSP(pos)/SP-C(pos) cells was observed, but the type II alveolar epithelial cells never recovered to baseline. CCSP(pos)/SP-C(pos) lung cells were stable until 7 months after birth. These cells in the BADJ primarily regenerate bronchiolar epithelial cells and not alveolar epithelial cells. Copyright © 2013 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  1. Structural and cellular changes in fetal renal papilla during development

    Directory of Open Access Journals (Sweden)

    Laura Vinci

    2017-02-01

    Full Text Available The mature renal papilla is characterized by medullary collecting ducts, Henle’s loops, vasa recta and the interstitium. Cortical and medullary stromal cells are essential for the regulation of urine concentration and other specialized kidney functions. Mechanisms that direct the renal papilla development are not clearly understood. In recent years, the renal papilla has been identified as a niche for renal stem/progenitor cells in the adult mouse. Studies on experimental animals evidenced a probably common interstitial progenitor for the medullary and cortical stromal cells, characterized by the Foxd1+/PAX2- phenotype. Moreover, Hox10 and Hox11 expression is required for differentiation and patterning of the multiple subtypes of developing medullary interstitial cells. Given the scarcity of morphological and molecular studies on the human renal papilla, this work aimed to evidence morphological changes during human gestation, both in the architecture of the medullary interstitium and in cell types differentiating between the collecting tubules and the Henle’s loops. Future immunohistochemical studies are needed to better identify different interstitial cell types giving rise to the mature interstitium of the renal papilla.

  2. Major enzymes controlling the androgenic pressure in the developing lung.

    Science.gov (United States)

    Tremblay, Yves; Provost, Pierre R

    2013-09-01

    A sex difference is observed in the incidence and morbidity of respiratory distress syndrome (RDS) of the neonate and in bronchopulmonary dysplasia (BPD). The involvement of androgens is well evidenced in RDS and it is suspected in BPD. Interestingly, the developing lung is not an inert tissue just exposed to circulating androgens, but is rather an active androgen metabolizing tissue, expressing enzymes involved in both androgen synthesis and inactivation. The present review focuses on the major enzymes involved in androgen metabolism within the developing lung. Testosterone synthesis and inactivation by AKR1C3/Akr1c6 (human/mouse 17β-hydroxysteroid dehydrogenases (HSDs) type 5) and HSD17B2 (17β-HSD type 2), respectively, play an important role in the developing lung. Akr1c14 (3α-HSD) shows a strong increase in expression according to developmental time. The canalicular stage of lung development corresponding to the surge of surfactant lipid synthesis, which is linked to RDS, as well as saccularization/alveolarization, which are linked to BPD, are covered by this review for the mouse and human species. The androgen metabolizing enzymes expressed within the developing lung can become potential pharmaceutical targets in the objective of accelerating lung maturation by specific treatments. The classic deleterious effects of androgens on lung maturation and the surge of surfactant synthesis in males are well known. Conversely, androgens also have positive impacts on the development of both male and female lungs. Steroidogenic enzymes are key regulators of these positive effects. This article is part of a Special Issue entitled 'CSR 2013'.

  3. [Fetal magnetocardiography].

    Science.gov (United States)

    van Leeuwen, P

    1997-09-01

    demonstrate the potential of the method in the examination of the fetal conductive system, arrhythmias, congential defects, growth, development of the autonomic system, acidosis and distress. Furthermore, first results in pathological cases indicate that it may become a valuable tool in prenatal diagnostics. Improvements in instrumentation as well as prospective multicenter studies with larger numbers of appropriate subjects are required to determine whether magnetocardiography will establish itself as a new tool in clinical fetal, surveillance.

  4. Doppler de las arterias pulmonares fetales posterior al uso de betametasona para la maduración pulmonar (Fetal lung arteries Doppler after to use of betamethasone for lung maturation)

    National Research Council Canada - National Science Library

    Keibis Jiménez Castillejo; Yolima Ruiz Lopez; Eduardo Reyna Villasmill; Duly Torres Cepeda; Joel Santos Bolívar; Jhoan Aragón Charry; Jorly Mejia Montilla; Nadia Reyna Villasmil

    2014-01-01

    Resumen (español) El objetivo de la investigación fue determinar las modificaciones del Doppler de las arterias pulmonares fetales posterior al uso de betametasona para la maduración pulmonar. Se realizó una...

  5. Psychoneuroimmunology in Pregnancy: Immune Pathways Linking Stress with Maternal Health, Adverse Birth Outcomes, and Fetal Development

    Science.gov (United States)

    Christian, Lisa M.

    2011-01-01

    It is well-established that psychological stress promotes immune dysregulation in nonpregnant humans and animals. Stress promotes inflammation, impairs antibody responses to vaccination, slows wound healing, and suppresses cell-mediated immune function. Importantly, the immune system changes substantially to support healthy pregnancy, with attenuation of inflammatory responses and impairment of cell-mediated immunity. This adaptation is postulated to protect the fetus from rejection by the maternal immune system. Thus, stress-induced immune dysregulation during pregnancy has unique implications for both maternal and fetal health, particularly preterm birth. However, very limited research has examined stress-immune relationships in pregnancy. The application of psychoneuroimmunology research models to the perinatal period holds great promise for elucidating biological pathways by which stress may affect adverse pregnancy outcomes, maternal health, and fetal development. PMID:21787802

  6. Psychoneuroimmunology in pregnancy: immune pathways linking stress with maternal health, adverse birth outcomes, and fetal development.

    Science.gov (United States)

    Christian, Lisa M

    2012-01-01

    It is well-established that psychological stress promotes immune dysregulation in nonpregnant humans and animals. Stress promotes inflammation, impairs antibody responses to vaccination, slows wound healing, and suppresses cell-mediated immune function. Importantly, the immune system changes substantially to support healthy pregnancy, with attenuation of inflammatory responses and impairment of cell-mediated immunity. This adaptation is postulated to protect the fetus from rejection by the maternal immune system. Thus, stress-induced immune dysregulation during pregnancy has unique implications for both maternal and fetal health, particularly preterm birth. However, very limited research has examined stress-immune relationships in pregnancy. The application of psychoneuroimmunology research models to the perinatal period holds great promise for elucidating biological pathways by which stress may affect adverse pregnancy outcomes, maternal health, and fetal development.

  7. Effect of water temperature on exercise-induced maternal hyperthermia on fetal development in rats.

    Science.gov (United States)

    Mottola, M F; Fitzgerald, H M; Wilson, N C; Taylor, A W

    1993-07-01

    The objective of this study was to determine if water temperature influenced exercise-induced hyperthermia in swim-trained pregnant rats and the resulting fetal development. Pregnant Sprague-Dawley rats with 6 weeks pre-pregnancy training were exercised daily from day 1 to day 18 of gestation in water that was 34.6 +/- 0.4 degrees C (Cool Water Swimmers--CWS) or 37.6 +/- 0.1 degrees C (Warm Water Swimmers--WWS), for one hour/day. During this time period another group of pregnant rats was immersed to the neck in warm water (37.6 +/- 0.2 degrees C) (Warm Water Controls--WWC). On day 19 of gestation all animals were sacrificed and fetal development assessed. Maternal exercise in warm water elevated maternal body core temperature by 2.3 +/- 0.1 degrees C above resting values, with an increase in fetal abnormalities compared to the same exercise intensity in cool water. Fifty-eight percent of the abnormal fetuses and 60% of the resorption sites were found in the WWS group. Of the abnormalities determined, 65% were from the WWS group and 45% of these fetuses showed micrencephaly. Results suggest cool water may regulate maternal body temperature during swimming exercise and that swimming in warm water should be avoided during gestation because of potential teratogenic effects.

  8. Development of the Endocrine Pancreas in the Beagle Dog: From Fetal to Adult Life.

    Science.gov (United States)

    Bricout-Neveu, Emilie; Pechberty, Severine; Reynaud, Karine; Maenhoudt, Cindy; José Lecomte, Marie; Ravassard, Philippe; Czernichow, Paul

    2017-03-14

    Our objectives were to describe, in Beagle dogs, the ontogenesis of beta (insulin-producing) and alpha (glucagon-producing) cells from fetal to early postnatal life and adulthood. In addition, to have some insight into interspecies comparison, Beagle dog pancreases were compared to pancreases from a Labrador and Chow Chow. At midgestation, the epithelium was dense, beta cells scarce, and alpha cells numerous and concentrated in the center of the pancreatic bud. From 36 to 45 days post conception (pc), beta cell numbers increased and the epithelium expanded and branched out. At 55 days pc, large beta cell aggregates were seen. At weaning, the islets were similar to those in adults, with limited alpha cells intermingled with numerous beta cells. Quantification of the Alpha to Beta cells ratio has shown a gradual increase of beta cells proportion throughout development. Similar findings were obtained in the 2 other breeds. In conclusion, in the fetal Beagle dog beta cells emerge from the pancreatic bud at midgestation, but the endocrine structure is mature only in early postnatal life. The ontogenesis of the endocrine pancreas demonstrated in dogs resembles that reported in rats and mice. In contrast, human beta cells appear earlier, at the beginning of the second trimester of gestation. Our study provides a detailed morphological description of pancreatic development in dogs but supplies no information on alpha- or beta-cell function during fetal life. The morphological data reported here provide a foundation for building physiological studies. This article is protected by copyright. All rights reserved.

  9. The carnivore pregnancy: the development of the embryo and fetal membranes.

    Science.gov (United States)

    Miglino, Maria Angelica; Ambrósio, Carlos Eduardo; dos Santos Martins, Daniele; Wenceslau, Cristiane Valverde; Pfarrer, Christiane; Leiser, Rudolf

    2006-10-01

    The aim of this research was to compare the morphological aspects during the development of pregnancy in dogs and cats, distinguishing features of the fetal membranes, such as yolk sac evolution and differentiation of hemangioblasts, and the degree of elaboration of the amnion and allantois. Canine and feline placentae from 20, 24, 35, 45 and 55 d of pregnancy were perfusion-fixed for histological investigation and vascular corrosion casts were produced. The casts were prepared for scanning electron microscopy (SEM) and the embryo and fetal membrane development was analyzed. The growth patterns of the conceptuses were compared with the organization of the placentation process, and changes of the morphology during pregnancy were recorded. In feline placentae, an incomplete zonary shape was present in 62.5% out of 60 studied cases. This was located distal to the insertion of the umbilical cord. In the lamellar zone, the interhemal membrane or placental barrier resembled endotheliochorial conditions, and the maternal-fetal microvascular blood flow interrelationship was of simple crosscurrent type. Dogs have a zonary placenta, completely surrounding the fetus, and complex lamellar organization of maternal and fetal tissues. At the border, two marginal hematomes with green colouration delimited the central placental girdle. The yolk sac consisted of one large sacculation with an inverted "T" shape and an enormous number of blood vessels; it had hemangioblast cells in contact with the epithelium. The amnion was avascular in early stages, but became vascularized by blood vessels of the internal allantoic membrane in later stages of pregnancy by intrinsic relation.

  10. In utero tractography of fetal white matter development.

    Science.gov (United States)

    Kasprian, Gregor; Brugger, Peter C; Weber, Michael; Krssák, Martin; Krampl, Elisabeth; Herold, Christian; Prayer, Daniela

    2008-11-01

    Diffusion tensor imaging (DTI) and tractography are noninvasive tools that enable the study of three-dimensional diffusion characteristics and their molecular, cellular, and microstructural correlates in the human brain. To date, these techniques have mainly been limited to postnatal MR studies of premature infants and newborns. The primary aim of this cross-sectional study was to assess the potential of in utero DTI and tractography to visualize the main projection and commissural pathways in 40 living, non-sedated human fetuses between 18 and 37 gestational weeks (GW) of age, with no structural brain pathologies. During a mean time of 1 min and 49 s, an axial, single-shot, echo planar DT sequence, with 32 diffusion gradient encoding directions and a reconstructed voxel size of 1.44 mm/1.45 mm/4.5 mm, was acquired. Most (90%) of the fetuses were imaged in the cephalic presentation. In 40% of examined fetuses, DTI measurements were robust enough to successfully calculate and visualize bilateral, craniocaudally oriented (mainly sensorimotor), and callosal trajectories in utero. Furthermore, fiber lengths, ADC, FA, and eigenvalues (lambda(1), lambda(2) and lambda(3)) were determined at different anatomically defined areas. FA values and the axial eigenvalue (lambda(1)) showed a characteristic distribution, with the highest values for the splenium, followed by the genu, the right, and the left posterior limb of the internal capsule. The right-sided sensorimotor trajectories were found to be significantly longer than on the left side (p=0.007), reflecting higher right-sided lambda(1) values (14 cases vs. 9 cases). Based on the good correlation of these initial in utero tractography results with prior documented postmortem and ex utero DTI data, this new imaging technique promises new insights into the normal and pathological development of the unborn child.

  11. Development of quantitative Doppler indices for uteroplacental and fetal blood flow during the third trimester.

    Science.gov (United States)

    Joern, H; Funk, A; Goetz, M; Kuehlwein, H; Klein, A; Fendel, H

    1996-01-01

    The aim of our study was to describe the development of uteroplacental and fetal blood flow during the third trimester. Doppler examination was carried out on 393 uncomplicated pregnancies with uncomplicated term delivery. Using a pulsed color Doppler, we calculated the maximum systolic, mean and maximum end-diastolic velocity after correcting the angle of insonation. Patients under tocolysis or other medication influencing blood flow parameters were excluded from this cross-sectional study. Summarizing the results gained by Doppler ultrasound investigation of the uteroplacental and fetal blood vessels, we created quantiles as quantitative Doppler indices for the maximum systolic, mean (TAMX = time averaged maximum velocity) and maximum end-diastolic velocity. The following conclusions could be drawn: (1) resistance to the blood flow in the maternal portion of the placenta does not change during the third trimester; (2) resistance to the blood flow on the fetal side of the placenta decreases up to week 42 of gestation; (3) cerebral vascular resistance decreases constantly up to gestational week 42; and (4) vascular resistance to the blood flow of the kidney decreases only slightly during the third trimester. This study offers clinically important values for quantitative Doppler flow velocimetry for the first time. We hope that our findings improve the usefulness of Doppler ultrasound as a diagnostic tool in obstetrical management.

  12. Structural development of human brain white matter from mid-fetal to perinatal stage

    Science.gov (United States)

    Ouyang, Austin; Yu, Qiaowen; Mishra, Virendra; Chalak, Lina; Jeon, Tina; Sivarajan, Muraleedharan; Jackson, Greg; Rollins, Nancy; Liu, Shuwei; Huang, Hao

    2015-03-01

    The structures of developing human brain white matter (WM) tracts can be effectively quantified by DTI-derived metrics, including fractional anisotropy (FA), mean, axial and radial diffusivity (MD, AD and RD). However, dynamics of WM microstructure during very early developmental period from mid-fetal to perinatal stage is unknown. It is difficult to accurately measure microstructural properties of these WM tracts due to severe contamination from cerebrospinal fluid (CSF). In this study, high resolution DTI of fetal brains at mid-fetal stage (20 weeks of gestation or 20wg), 19 brains in the middle of 3rd trimester (35wg) and 17 brains around term (40wg) were acquired. We established first population-averaged DTI templates at these three time points and extracted WM skeleton. 16 major WM tracts in limbic, projection, commissural and association tract groups were traced with DTI tractography in native space. The WM skeleton in the template space was inversely transformed back to the native space for measuring core WM microstructures of each individual tract. Continuous microstructural enhancement and volumetric increase of WM tracts were found from 20wg to 40wg. The microstructural enhancement from FA measurement is decelerated in late 3rd trimester compared to mid-fetal to middle 3rd trimester, while volumetric increase of prefrontal WM tracts is accelerated. The microstructural enhancement from 35wg to 40wg is heterogeneous among different tract groups with microstructures of association tracts undergoing most dramatic change. Besides decreases of RD indicating active myelination, the decrease of AD for most WM tracts during late 3rd trimester suggests axonal packing process.

  13. Influence of cortisol on adipose tissue development in the fetal sheep during late gestation.

    Science.gov (United States)

    Mostyn, A; Pearce, S; Budge, H; Elmes, M; Forhead, A J; Fowden, A L; Stephenson, T; Symonds, M E

    2003-01-01

    The present study examined the extent to which the late gestation rise in fetal plasma cortisol influenced adipose tIssue development in the fetus. The effect of cortisol on the abundance of adipose tIssue mitochondrial proteins on both the inner (i.e. uncoupling protein (UCP)1) and outer (i.e. voltage-dependent anion channel (VDAC)) mitochondrial membrane, together with the long and short forms of the prolactin receptor (PRLR) protein and leptin mRNA was determined. Perirenal adipose tIssue was sampled from ovine fetuses to which (i) cortisol (2-3 mg/day for 5 days) or saline was infused up to 127-130 days of gestation, and (ii) adrenalectomised and intact controls at between 142 and 145 days of gestation (term=148 days). UCP1 protein abundance was significantly lower in adrenalectomised fetuses compared with age-matched controls, and UCP1 was increased by cortisol infusion and with gestational age. Adrenalectomy reduced the concentration of the long form of PRLR, although this effect was only significant for the highest molecular weight isoform. In contrast, neither the short form of PRLR, VDAC protein abundance or leptin mRNA expression was significantly affected by gestational age or cortisol status. Fetal plasma triiodothyronine concentrations were increased by cortisol and with gestational age, an affect abolished by adrenalectomy. When all treatment groups were combined, both plasma cortisol and triiodothyronine concentrations were positively correlated with UCP1 protein abundance. In conclusion, an intact adrenal is necessary for the late gestation rise in UCP1 protein abundance but cortisol does not appear to have a major stimulatory role in promoting leptin expression in fetal adipose tIssue. It remains to be established whether effects on UCP1 protein are directly regulated by cortisol alone or mediated by other anabolic fetal hormones such as triiodothyronine.

  14. Ectopic expression of a small cell lung cancer transcription factor, INSM1 impairs alveologenesis in lung development

    OpenAIRE

    2016-01-01

    Background Insulinoma associated-1 (INSM1) gene is expressed exclusively in early embryonic neuroendocrine tissues, but has been found highly re-activated in most of the neuroendocrine tumors including small cell lung carcinoma. Methods In order to elucidate the functional effects of INSM1 in normal lung development, we used a conditional lung-specific INSM1 transgenic mouse model. Transgenic (Tet-on system) CMV-INSM1 responder mice were bred with the lung-specific, club cell secretory protei...

  15. Lung metastases

    Science.gov (United States)

    Metastases to the lung; Metastatic cancer to the lung; Lung cancer - metastases ... Metastatic tumors in the lungs are cancers that developed at other places in the body (or other parts of the lungs). They then spread through ...

  16. Effects of strenuous maternal exercise on fetal organ weights and skeletal muscle development in rats.

    Science.gov (United States)

    Mottola, M F; Bagnall, K M; Belcastro, A N

    1989-02-01

    The purpose of the present study was to observe the effects of strenuous maternal aerobic exercise throughout gestation on fetal outcome in the rat. The strenuous exercise intensity consisted of a treadmill speed of 30 m.min-1 on a 10 degrees incline, for 120 min.day-1, 5 days.week-1. The rats were conditioned to run on a motor-driven treadmill by following a progressive two-week exercise program, so that by the end of the two weeks the rats were capable of running comfortably at this strenuous intensity in the non-pregnant state. Following the two-week running programme, the rats were paired by weight and randomly assigned to either a pregnant group that continued the running program throughout gestation (pregnant runner), or a pregnant group that did not continue the running program throughout pregnancy (pregnant control). At birth the neonates born to the pregnant running group did not differ in average neonatal body weight values, number per litter or total litter weight values when compared to controls, nor were superficial gross abnormalities observed in neonates born to the pregnant control or pregnant running groups. The strenuous maternal exercise intensity did not alter neonatal organ weight values (brain, heart, liver, lung, kidney), nor neonatal skeletal muscle (gastrocnemius, sternomastoid, diaphragm) when compared to control values. It is suggested that maternal exercise of this intensity throughout gestation does not affect fetal outcome in the rat, and may be due to the animals accustomization to the strenuous exercise protocol prior to pregnancy.

  17. Development of lung cancer CT screening operating support system

    Science.gov (United States)

    Ishigaki, Rikuta; Hanai, Kozou; Suzuki, Masahiro; Kawata, Yoshiki; Niki, Noboru; Eguchi, Kenji; Kakinuma, Ryutaro; Moriyama, Noriyuki

    2009-02-01

    In Japan, lung cancer death ranks first among men and third among women. Lung cancer death is increasing yearly, thus early detection and treatment are needed. For this reason, CT screening for lung cancer has been introduced. The CT screening services are roughly divided into three sections: office, radiology and diagnosis sections. These operations have been performed through paper-based or a combination of paper-based and an existing electronic health recording system. This paper describes an operating support system for lung cancer CT screening in order to make the screening services efficient. This operating support system is developed on the basis of 1) analysis of operating processes, 2) digitalization of operating information, and 3) visualization of operating information. The utilization of the system is evaluated through an actual application and users' survey questionnaire obtained from CT screening centers.

  18. Fetal central nervous system development and alcohol--the evidence so far.

    Science.gov (United States)

    Ahmed-Landeryou, Musharrat Jabeen

    2012-12-01

    Currently in the UK, there is no absolute guidance about alcohol consumption in pregnancy. The guidance for drinking during pregnancy is one or two units of alcohol one or two times weekly, but conservative advice is to abstain as a cautionary measure. Despite the lack of consensus about the safe levels of alcohol consumption in pregnancy, there is increasing evidence of the impact of alcohol on the developing central nervous system. This article explores the evidence regarding alcohol consumption and its effects on the developing fetal central nervous system.

  19. Study of fetal lung volume using virtual organ computer aided analytical technique%三维超声体积自动测量技术对胎儿肺体积的研究

    Institute of Scientific and Technical Information of China (English)

    陈骊珠; 王晓光; 蔡爱露; 王冰

    2012-01-01

    Objective: To evaluate the correlation between fetal lung volumes and gestational age, and estimated fetal weight, and to evaluate the potential diagnostic value of ultrasound fetal lung to body weight ratio (UFLB) in fetal pulmonary hypoplasia (PH). Methods: The fetal lung volumes were assessed in 315 normal fetuses and 28 fetuses with high risk of PH using the technique of virtual organ computer-aided analysis (VOCAL). The relationships between the lung volumes and gestational age, and fetal weight were assessed by correlation and regression analysis. The value of UFLB in the diagnosis of fetal PH was acquired by compared with the postnatal findings. Results: Fetal lung volumes were highly correlated with gestational age(r=0.93,P<0.05), and with fetal weight(r=0.97,P<0.05). The sensitivity, specificity, positive and negative predictive values of UFLB in diagnosing fetal PH was 89.47%, 85.71%, 94.44% and 75.00%, respectively, and the accuracy was 88.46%. Conclusion: In normal fetuses, fetal lung volumes increase with gestational age and fetal weight. UFLB may be useful in the prenatal diagnosis of fetal PH.%目的:探讨正常孕中晚期胎儿肺体积随孕周、胎儿体重的变化规律,以及超声肺重比(UFLB)对胎儿肺发育不良(PH)的诊断价值.方法:超声检查315例正常胎儿和28例PH高危胎儿,应用三维超声体积自动测量(VOCAL)技术测量胎儿肺体积,采用二维超声测得的生物参数经Hadlock方程系统获得胎儿质量,计算得到胎儿UFLB,随访胎儿产后及引产结果,并与产前诊断结果作对照.结果:正常胎儿肺体积与胎儿质量(r=0.97,P<0.05)的相关性高于胎儿肺体积与孕周(r=0.93,P<0.05)的相关性.28例PH高危胎儿中,2例因羊水过少未能获得满意的三维图像,PH高危胎儿应用VOCAL技术获得肺体积的成功率为92.90%.在成功获得肺体积的26例胎儿中,应用UFLB诊断胎儿PH的敏感度为89.47%,特异度为85.71%,阳性预测值为94.44

  20. Ochratoxin A and T-2 Toxin Induce Clonogenicity and Cell Migration in Human Colon Carcinoma and Fetal Lung Fibroblast Cell Lines.

    Science.gov (United States)

    Abassi, Haila; Ayed-Boussema, Imen; Shirley, Sarah; Abid, Salwa; Bacha, Hassen

    2016-03-01

    T-2 toxin and Ochratoxin A (OTA) are toxic secondary metabolites produced by various fungi, and together they contaminate feedstuffs worldwide. T-2 toxin and OTA may exert carcinogenic action in rodent. Despite the various in vivo experiments, carcinogenicity of these two mycotoxins has not yet been proven for human. In this current study, we proposed to investigate, in Human colon carcinoma cells and fetal lung fibroblast-like cells transfected with MYC, the effect of T-2 toxin and OTA on cell clonogenicity and cell migration. Results of the present investigation showed that T2-toxin as well as OTA has an important clonogenic effect in all cell lines, suggesting that these mycotoxins could promote the transcription of c-myc gene. Furthermore, T-2 toxin and OTA enhanced the migration effect of HCT116 cells at very low concentrations, proposing that these mycotoxins may exhibit carcinogenesis-like properties in the studied cells.

  1. Involvement of the SLIT/ROBO pathway in follicle development in the fetal ovary.

    Science.gov (United States)

    Dickinson, Rachel E; Hryhorskyj, Lynn; Tremewan, Hannah; Hogg, Kirsten; Thomson, Axel A; McNeilly, Alan S; Duncan, W Colin

    2010-02-01

    In humans and domestic mammals, pivotal processes in ovary development, including primordial follicle assembly, occur prenatally. These events are essential for determining fertility in adult life; however, they remain poorly understood at the mechanistic level. In mammals, the SLITs (SLIT1, SLIT2 and SLIT3) and their ROBO (ROBO1, ROBO2, ROBO3/RIG-1 and ROBO4/MAGIC ROBO) receptors regulate neural, leukocyte, vascular smooth muscle cell and endothelial cell migration. In addition, the SLIT/ROBO pathway has functional roles in embryonic development and in the adult ovary by inhibiting cell migration and promoting apoptosis. We therefore characterised follicle formation and investigated the expression and localisation of the ROBO/SLIT pathway in the ovine fetal ovary. Using RT-PCR, we identified SLIT2, SLIT3, ROBO1, ROBO2 and ROBO4 in sheep ovaries harvested across gestation. The real-time quantitative PCR results implied that ROBO2 expression and ROBO4 expression were elevated during the early stages of follicle formation and stayed abundant during primordial follicle maturation (PROBO1 was localised to the pre-granulosa cells, while ROBO2, ROBO4 and SLIT2 were expressed in the oocytes of the developing primordial follicle. This indicates that in the fetal ovary, SLIT-ROBO signalling may require an autocrine and paracrine interaction. Furthermore, at the time of increased SLIT-ROBO expression, there was a significant reduction in the number of proliferating oocytes in the developing ovary (PROBO pathway is expressed at the time of follicle formation during fetal ovary development.

  2. Echocardiographic Assessment of Embryonic and Fetal Mouse Heart Development: A Focus on Haemodynamics and Morphology

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    Nathan D. Hahurij

    2014-01-01

    Full Text Available Background. Heart development is a complex process, and abnormal development may result in congenital heart disease (CHD. Currently, studies on animal models mainly focus on cardiac morphology and the availability of hemodynamic data, especially of the right heart half, is limited. Here we aimed to assess the morphological and hemodynamic parameters of normal developing mouse embryos/fetuses by using a high-frequency ultrasound system. Methods. A timed breeding program was initiated with a WT mouse line (Swiss/129Sv background. All recordings were performed transabdominally, in isoflurane sedated pregnant mice, in hearts of sequential developmental stages: 12.5, 14.5, and 17.5 days after conception (n=105. Results. Along development the heart rate increased significantly from 125 ± 9.5 to 219 ± 8.3 beats per minute. Reliable flow measurements could be performed across the developing mitral and tricuspid valves and outflow tract. M-mode measurements could be obtained of all cardiac compartments. An overall increase of cardiac systolic and diastolic function with embryonic/fetal development was observed. Conclusion. High-frequency echocardiography is a promising and useful imaging modality for structural and hemodynamic analysis of embryonic/fetal mouse hearts.

  3. Fetal Exposure to Sertraline Hydrochloride Impairs Pancreatic β-Cell Development.

    Science.gov (United States)

    De Long, Nicole E; Gutgesell, Marie K; Petrik, James J; Holloway, Alison C

    2015-06-01

    Ten percent to 15% of women take selective serotonin reuptake inhibitor (SSRI) antidepressants during pregnancy. Offspring exposed to SSRIs are more likely to have low birth weight; this is associated with an increased risk of development of diabetes in adulthood in part due to altered pancreatic development. The effects of perinatal exposure to SSRIs on pancreatic development are unknown. Therefore, the objective of this study was to determine the effect of fetal exposure to sertraline hydrochloride on pregnancy outcomes and pancreatic development. Wistar rats were given vehicle (n = 5) or sertraline hydrochloride (10 mg/kg/d; n = 8) via daily subcutaneous injection from the confirmation of mating until parturition. Results from this animal model demonstrated that offspring born to sertraline-exposed dams have no changes in birth weight but had a reduction in pancreatic β-cell area. The altered pancreatic islet development was a result of altered gene expression regulating islet development and survival. Therefore, fetal exposure to sertraline reduces β-cell capacity at birth, raising concerns regarding the long-term metabolic sequelae of such exposures.

  4. Histomorphological evaluation of the digital coronary region at different fetal development stages of Holstein cattle

    Directory of Open Access Journals (Sweden)

    R.E. Rabelo

    2015-02-01

    Full Text Available The scientific literature lacks detailed morphological descriptions of the histological development and cell differentiation of fetal bovine hoof. In this study, 40 extremity members of Holstein bovine fetuses were collected and divided into four groups (G1 to G4 based on the estimated age. Fragments were removed from wall and sole, processed and stained with hematoxylin - eosin (HE for light microscopy observation. In G1, it was found that the epidermis was very thin, including keratinocyte layers and clusters of mesenchymal cells. In group G2 it was observed that the thickness of the epidermis covering the limbs remained variable and laminar corium developed in the germinal layer. In group G3 it was noted that in the germinal epithelium there were papillae in little advanced development and cells of the stratum corneum in the initial process of keratinization. In G4, the epidermis was well developed with layers distributed homogeneously, containing symmetrical and long papillae and intense production of keratin. In this work, the most important cellular events for the formation of the fetal hoof in Holstein cattle were first described in different stages of their formation.

  5. Periconceptional growth hormone treatment alters fetal growth and development in lambs.

    Science.gov (United States)

    Koch, J M; Wilmoth, T A; Wilson, M E

    2010-05-01

    Research in the area of fetal programming has focused on intrauterine growth restriction. Few studies have attempted to examine programming mechanisms that ultimately lead to lambs with a greater potential for postnatal growth. We previously demonstrated that treatment of ewes with GH at the time of breeding led to an increase in birth weight. Therefore, the objective of this study was to determine the effects of a single injection of sustained-release GH given during the periconceptional period on fetal growth and development and to determine if the GH axis would be altered in these offspring. Estrus was synchronized using 2 injections of PGF(2alpha); at the time of the second injection, ewes assigned to treatment were also given an injection of sustained-release GH. A maternal jugular vein sample was taken weekly to analyze IGF-I as a proxy for GH to estimate the duration of the treatment effect. In ewes treated with GH, IGF-I increased (P growth and development. Lambs born to ewes treated with GH were larger at birth and had altered organ development, which may indicate that early maternal GH treatment may lead to permanent changes in the developing fetus. The ewe lambs maintained their growth performance to at least 100 d of postnatal life and appeared to have an altered GH axis, as demonstrated by the altered response to GHRH.

  6. Development of a three-dimensional model of lung cancer using cultured transformed lung cells.

    Science.gov (United States)

    Vertrees, Roger A; McCarthy, Maureen; Solley, Travis; Popov, Vselovod L; Roaten, John; Pauley, Matthew; Wen, Xiaodong; Goodwin, Thomas J

    2009-02-01

    Despite great strides in understanding cancer biology, the role cellular differentiation and three-dimensional (3-D) structural organization play in metastasis and malignancy remains unclear. Development of 3-D cultures may ultimately provide a model facilitating discovery and interpretation of more relevant information for the expression and role of antibodies in lung cellular pathobiology. The purpose was to develop traditional monolayer (ML) and 3-D cultures of a known transformed metastatic lung cell line and then determine similarities and differences between cultures in terms of differentiation, molecular marker expression and metastasis. A transformed lung cell line (BZR-T33) was initially transfected with green fluorescent protein (GFP) in ML culture. Nude mice were inoculated with BZR-T33 and observed for metastasis. BZR-T33 was grown as ML and 3-D cultures under identical conditions. Immunohistochemical comparison for degree of antibody expression between cultures and control tissue were studied. Electron microscopy (EM) for identification of ultra structures was done and compared between cultures. A 3-D co-culture containing GFP-transformed cells over an immortalized lung-cell line was developed. The GFP-transfected cell line formed tumors and metastasized in mice. EM identified significant mitochondrial and granular endoplasmic reticular pathology in ML not seen in 3-D. Degree of differentiation shows ultra structures and antibody expressions were more representative of control tissue in 3-D than ML. The co-culture experiment in 3-D demonstrates the ability of transformed cells to penetrate the sub-layer of immortalized cells. Development of 3-D cultures will provide a new and powerful tool to study lung biology and pathobiology.

  7. Fetal MRI detects early alterations of brain development in Tetralogy of Fallot.

    Science.gov (United States)

    Schellen, Christoph; Ernst, Schwartz; Gruber, Gerlinde M; Mlczoch, Elisabeth; Weber, Michael; Brugger, Peter C; Ulm, Barbara; Langs, Georg; Salzer-Muhar, Ulrike; Prayer, Daniela; Kasprian, Gregor

    2015-09-01

    Prenatal imaging has identified alterations of brain growth in fetuses with congenital heart disease. However, little is known about the timing of altered brain development and its occurrence in specific congenital heart disease subgroups. This magnetic resonance imaging study aimed to identify early (median, 25 gestational weeks [GW]) changes in fetal total brain (TBV), gray matter (GMV), and subcortical brain (SBV) volumes in Tetralogy of Fallot (TOF) cases in utero. Fetal magnetic resonance imaging (1.5 Tesla) was performed in 24 fetuses who were diagnosed with TOF and 24 normal age-matched control fetuses (20-34 GW). TBV, GMV, SBV, intracranial cavity, cerebellar, ventricular, and external cerebrospinal fluid volumes were quantified by manual segmentation based on coronal T2-weighted sequences. Mixed model analyses of variance and t-tests were conducted to compare cases and control fetuses. TBV was significantly lower (P < .001) in early (<25 GW) and late TOF cases. Both GMV (P = .003) and SBV (P = .001) were affected. The GMV-to-SBV ratio declined in fetuses with TOF (P = .026). Compared with normal fetuses, ventricular volume was increased (P = .0048). External cerebrospinal fluid was enlarged in relation to head size (P < .001). Intracranial cavity volume (P = .314) and cerebellar volume (P = .074) were not significantly reduced in fetuses with TOF. TOF is associated with smaller volumes of gray and white matter and enlarged cerebrospinal fluid spaces. These changes are present at ≤25 GW and indicate altered fetal brain growth in this pathophysiologic entity during early stages of human brain development. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Pigment epithelium-derived factor mediates impaired lung vascular development in neonatal hyperoxia.

    Science.gov (United States)

    Chetty, Anne; Bennett, Michelle; Dang, Linh; Nakamura, Daisy; Cao, Gong-Jie; Mujahid, Sana; Volpe, MaryAnn; Herman, Ira; Becerra, S Patricia; Nielsen, Heber C

    2015-03-01

    Bronchopulmonary dysplasia is a chronic lung disease of preterm infants characterized by arrested microvascularization and alveolarization. Studies show the importance of proangiogenic factors for alveolarization, but the importance of antiangiogenic factors is unknown. We proposed that hyperoxia increases the potent angiostatin, pigment epithelium-derived factor (PEDF), in neonatal lungs, inhibiting alveolarization and microvascularization. Wild-type (WT) and PEDF(-/-) mice were exposed to room air (RA) or 0.9 fraction of inspired oxygen from Postnatal Day 5 to 13. PEDF protein was increased in hyperoxic lungs compared with RA-exposed lungs (P epithelium. Hyperoxia reduced alveolarization in WT mice (P lung microvascularization by vascular endothelial growth factor and PEDF was studied in vitro using MFLM-91U cells, a fetal mouse lung endothelial cell line. Vascular endothelial growth factor stimulation of proliferation, migration, and capillary tube formation was inhibited by PEDF. MFLM-91U cells exposed to conditioned medium (CM) from E17 fetal mouse lung type II (T2) cells cultured in 0.9 fraction of inspired oxygen formed fewer capillary tubes than CM from T2 cells cultured in RA (hyperoxia CM, 51 ± 10% of RA CM, P < 0.05), an effect abolished by PEDF antibody. We conclude that PEDF mediates reduced vasculogenesis and alveolarization in neonatal hyperoxia. Bronchopulmonary dysplasia likely results from an altered balance between pro- and antiangiogenic factors.

  9. Esophageal cancer developed 13 years after radiotherapy for lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Okazaki, Atsushi; Matsuura, Masana; Noda, Masanobu; Katsumata, Yasushi; Maehara, Tadayuki; Tamura, Shizuo; Uzawa, Takeshi; Ishikawa, Toshitaka

    1988-05-01

    This paper reports on an autopsied case manifesting an esophageal cancer that had developed 13 years after radiotherapy for lung cancer. The patient was a 61-year-old man. He was found to have a squamous cell carcinoma of the right lower bronchus with a swelling of the mediastinal and left supraclavicular lymph nodes in July of 1973. He received 60 Gy of irradiation in the right lung, the mediastinum, and the left supraclavicular region. Later, after doing well until August of 1986, a squamous cell carcinoma of the esophagus was found at the upper intrathoracic site. Thus, he also received additional radiotherapy but died of pneumonia after this local recurrence 7 months later. At autopsy, no local recurrence of the primary lung cancer was found. The site of esophageal cancer was far from that of the primary lung cancer thought it was included in the previous treatment ports. This suggests the possibility that the primary esophageal cancer had been induded by therapeutic irradiation. So far as we know, this is the first report of esophageal cancer that may have developed after irradiation for lung cancer.

  10. [Esophageal cancer developing 13 years after radiotherapy of lung cancer].

    Science.gov (United States)

    Okazaki, A; Matsuura, M; Noda, M; Katsumata, Y; Maehara, T; Tamura, S; Uzawa, T; Ishiko, T

    1988-05-01

    This paper reports on an autopsied case manifesting an esophageal cancer that had developed 13 years after radiotherapy for lung cancer. The patient was a 61-year-old man. He was found to have a squamous cell carcinoma of the right lower bronchus with a swelling of the mediastinal and left supraclavicular lymph nodes in July of 1973. He received 60 Gy of irradiation in the right lung, the mediastinum, and the left supraclavicular region. Later, after doing well until August of 1986, a squamous cell carcinoma of the esophagus was found at the upper intrathoracic site. Thus, he also received additional radiotherapy but died of pneumonia after this local recurrence 7 months later. At autopsy, no local recurrence of the primary lung cancer was found. The site of esophageal cancer was far from that of the primary lung cancer though it was included in the previous treatment ports. This suggests the possibility that the primary esophageal cancer had been induced by therapeutic irradiation. So far as we know, this is the first report of esophageal cancer that may have developed after irradiation for lung cancer.

  11. Antimicrobial efficacy against Pseudomonas aeruginosa biofilm formation in a three-dimensional lung epithelial model and the influence of fetal bovine serum

    Science.gov (United States)

    Crabbé, Aurélie; Liu, Yulong; Matthijs, Nele; Rigole, Petra; De La Fuente-Nùñez, César; Davis, Richard; Ledesma, Maria A.; Sarker, Shameema; Van Houdt, Rob; Hancock, Robert E. W.; Coenye, Tom; Nickerson, Cheryl A.

    2017-01-01

    In vitro models that mimic in vivo host-pathogen interactions are needed to evaluate candidate drugs that inhibit bacterial virulence traits. We established a new approach to study Pseudomonas aeruginosa biofilm susceptibility on biotic surfaces, using a three-dimensional (3-D) lung epithelial cell model. P. aeruginosa formed antibiotic resistant biofilms on 3-D cells without affecting cell viability. The biofilm-inhibitory activity of antibiotics and/or the anti-biofilm peptide DJK-5 were evaluated on 3-D cells compared to a plastic surface, in medium with and without fetal bovine serum (FBS). In both media, aminoglycosides were more efficacious in the 3-D cell model. In serum-free medium, most antibiotics (except polymyxins) showed enhanced efficacy when 3-D cells were present. In medium with FBS, colistin was less efficacious in the 3-D cell model. DJK-5 exerted potent inhibition of P. aeruginosa association with both substrates, only in serum-free medium. DJK-5 showed stronger inhibitory activity against P. aeruginosa associated with plastic compared to 3-D cells. The combined addition of tobramycin and DJK-5 exhibited more potent ability to inhibit P. aeruginosa association with both substrates. In conclusion, lung epithelial cells influence the efficacy of most antimicrobials against P. aeruginosa biofilm formation, which in turn depends on the presence or absence of FBS. PMID:28256611

  12. Expression of Extracellular Matrix Proteins in Basal Membranes During Fetal Nephron Development in Mice

    Directory of Open Access Journals (Sweden)

    Beyhan GÜRCÜ

    2016-04-01

    Full Text Available In this study, we investigated the distribution of laminin, collagen type IV, nidogen and fibronectine during metanephric development in fetal mouse kidney by immunohistochemistry. Stain density of basement membranes of tubules, glomerules and mesangial matrix were compared in pre-capillary, immature glomerular and mature glomerular stages of fetal kidney. All the matrix proteins were strongly stained in precapillary stage. In immature glomerular stage, a strong staining was observed for fibronectin. Staining intensity was slightly decreased for the other proteins in this stage. In mature glomerular stage, diminished staining for all proteins was observed similar to the previous stage, except fibronectin. The strongest immunoreactions were found for fibronectin and nidogen in all investigated stages. In general, there was a similar staining intensity for all glycoproteins during maturation except for laminin. It was thought that the distribution of extracellular matrix molecules plays an important role for the kidney development. Interactions amoung these molecules probably crucial on cell behavior like migration, proliferation and differentiation in normal development of the nephron.

  13. MicroRNAs and fetal brain development: Implications for ethanol teratology during the second trimester period of neurogenesis.

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    Rajesh eMiranda

    2012-05-01

    Full Text Available Maternal ethanol consumption during pregnancy can lead to a stereotypic cluster of fetal craniofacial, cardiovascular, skeletal and neurological deficits that are collectively termed the Fetal Alcohol Spectrum Disorder (FASD. Fetal ethanol exposure is a leading non-genetic cause of mental retardation. Mechanisms underlying the etiology of ethanol teratology are varied and complex. This review will focus on the developing brain as an important and vulnerable ethanol target. Near the end of the first trimester, and during the second trimester, fetal neural stem cells (NSCs produce most of the neurons of the adult brain, and ethanol has been shown to influence NSC renewal and maturation. We will discuss the neural developmental and teratological implications of the biogenesis and function of microRNAs (miRNAs, a class of small non-protein-coding RNAs that control the expression of gene networks by translation repression. A small but growing body of research has identified ethanol-sensitive miRNAs at different stages of NSC and brain maturation. While many microRNAs appear to be vulnerable to ethanol at specific developmental stages, a few, like the miR-9 family, appear to exhibit broad vulnerability to ethanol across multiple stages of NSC differentiation. An assessment of the regulation and function of these miRNAs provides important clues about the mechanisms that underlie fetal vulnerability to alterations in the maternal-fetal environment and yields insights into the genesis of FASD.

  14. Molecular mechanism of carvedilol in attenuating the reversion to fetal energy metabolism during cardiac hypertrophy development

    Institute of Scientific and Technical Information of China (English)

    胡琴; 李隆贵

    2003-01-01

    Objective: To explore the molecular regulation mechanism of carvedilol in attenuating the reversion back towards fetal energy metabolism during the development of cardiac hypertrophy induced by coarctation of abdominal aorta (CAA) in male Wistar rats. Methods: Hemodynamic and ventricular remodeling parameters, free fatty acid content in the serum were measured in the experimental animals at 16 weeks after the surgical CAA, the rats receiving carvedilol intervention (CAR) after CAA, and those with sham operation (SH). The expressions of muscle carnitine palmitoyltransferaseⅠ (M-CPTⅠ) and medium chain acyl-CoA dehydrogenase (MCAD) mRNA in the cardiac myocytes from every group were studied with RT-PCR. Results: Significant left ventricular hypertrophy were observed in the rats 16 weeks after coarctation operation (P<0.05), together with significant free fatty acids accumulation and downregulation of M-CPTⅠ and MCAD mRNA (P<0.05) in CAA group. Carvedilol at a dose of 30 mg/kg/d for 12 weeks inhibited the left ventricular hypertrophy induced by pressure overload and enhanced the gene expressions of rate-limiting enzyme (M-CPTⅠ) and key enzyme of fatty acid (MCAD) in the CAR group compared with CAA group (P<0.05). Conclusion: Pressure overload-induced hypertrophy in CAA rats causes the reversion back towards fetal enery metabolism, that is, downregulates the expressions of rate-limiting enzyme and key enzyme of fatty acid oxidation. The intervention therapy with carvedilol, a vasodilating alpha- and beta-adrenoreceptor antagonist, attenuates the reversion of the metabolic gene expression to fetal type through upregulating M-CPTⅠ and MCAD mRNA expressions. Thus, carvedilol may exert cardioprotective effects on heart failure by the mechanism of preserving the adult metabolic gene regulation.

  15. The effects of Love Canal soil extracts on maternal health and fetal development in rats.

    Science.gov (United States)

    Silkworth, J B; Tumasonis, C; Briggs, R G; Narang, A S; Narang, R S; Rej, R; Stein, V; McMartin, D N; Kaminsky, L S

    1986-10-01

    The effects of a solvent extract of the surface soil of the Love Canal chemical dump site, Niagara Falls, New York, and of a natural extract, or leachate, which is drained from the canal for treatment, on the maternal health and fetal development were determined in rats. The solvent extract, which was contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (2, 3,7,8-TCDD) at 170 ppb and numerous other chlorinated organic compounds with the primary identified components being the isomers of benzenehexachloride (BHC), was dissolved in corn oil and administered by gavage to pregnant rats at 0,25,75, or 150 mg crude extract/kg/day on Days 6-15 of gestation. A 67% mortality was observed at the highest dose. The rats were sacrificed on Day 20. Dose-related increases in relative liver weight accompanied by hepatocyte hypertrophy were observed at all dose levels. Fetal birthweight was decreased at 75 and 150 mg extract/kg/day. No major treatment-related soft tissue or skeletal malformations, except for delayed ossification, were observed. Based on literature values for BHC, all of the observed toxicity could be accounted for by the BHC contaminants of the extract. The crude organic phase of the leachate was administered to pregnant rats at 0,10,100, or 250 mg/kg/day as described above. Maternal weight gain decreased at 100 and 250 mg/kg/day, accompanied by 5 and 14% maternal mortality, and 1 and 3 dead fetuses, respectively. Early resorptions and the percentage of dead implants increased whereas fetal birthweights were decreased at 250 mg/kg/day. No major treatment-related soft tissue or skeletal malformations, except for delayed ossification, were observed. The primary components of the complex leachate by mass were tetrachloroethanes; however, 2,3,7,8-TCDD, which was present at 3 ppm, probably accounted for all the observed toxicity.

  16. Effects of Love Canal soil extracts on maternal health and fetal development in rats

    Energy Technology Data Exchange (ETDEWEB)

    Silkworth, J.B.; Tumasonis, C.; Briggs, R.G.; Narang, A.S.; Narang, R.S.; Rej, R.; Stein, V.; McMartin, D.N.; Kaminsky, L.S.

    1986-10-01

    The effects of a solvent extract of the surface soil of the Love Canal chemical dump site, Niagara Falls, New York, and of a natural extract, or leachate, which is drained from the canal for treatment, on the maternal health and fetal development were determined in rats. The solvent extract, which was contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (2, 3,7,8-TCDD) at 170 ppb and numerous other chlorinated organic compounds with the primary identified components being the isomers of benzenehexachloride (BHC), was dissolved in corn oil and administered by gavage to pregnant rats at 0,25,75, or 150 mg crude extract/kg/day on Days 6-15 of gestation. A 67% mortality was observed at the highest dose. The rats were sacrificed on Day 20. Dose-related increases in relative liver weight accompanied by hepatocyte hypertrophy were observed at all dose levels. Fetal birthweight was decreased at 75 and 150 mg extract/kg/day. No major treatment-related soft tissue or skeletal malformations, except for delayed ossification, were observed. Based on literature values for BHC, all of the observed toxicity could be accounted for by the BHC contaminants of the extract. The crude organic phase of the leachate was administered to pregnant rats at 0,10,100, or 250 mg/kg/day as described above. Maternal weight gain decreased at 100 and 250 mg/kg/day, accompanied by 5 and 14% maternal mortality, and 1 and 3 dead fetuses, respectively. Early resorptions and the percentage of dead implants increased whereas fetal birthweights were decreased at 250 mg/kg/day. No major treatment-related soft tissue or skeletal malformations, except for delayed ossification, were observed. The primary components of the complex leachate by mass were tetrachloroethanes; however, 2,3,7,8-TCDD, which was present at 3 ppm, probably accounted for all the observed toxicity.

  17. Fetal Circulation

    Science.gov (United States)

    ... Peripheral Artery Disease Venous Thromboembolism Aortic Aneurysm More Fetal Circulation Updated:Oct 18,2016 click to enlarge The ... fetal heart. These two bypass pathways in the fetal circulation make it possible for most fetuses to survive ...

  18. Fetal MRI: An approach to practice: A review

    Directory of Open Access Journals (Sweden)

    Sahar N. Saleem

    2014-09-01

    Full Text Available MRI has been increasingly used for detailed visualization of the fetus in utero as well as pregnancy structures. Yet, the familiarity of radiologists and clinicians with fetal MRI is still limited. This article provides a practical approach to fetal MR imaging. Fetal MRI is an interactive scanning of the moving fetus owed to the use of fast sequences. Single-shot fast spin-echo (SSFSE T2-weighted imaging is a standard sequence. T1-weighted sequences are primarily used to demonstrate fat, calcification and hemorrhage. Balanced steady-state free-precession (SSFP, are beneficial in demonstrating fetal structures as the heart and vessels. Diffusion weighted imaging (DWI, MR spectroscopy (MRS, and diffusion tensor imaging (DTI have potential applications in fetal imaging. Knowing the developing fetal MR anatomy is essential to detect abnormalities. MR evaluation of the developing fetal brain should include recognition of the multilayered-appearance of the cerebral parenchyma, knowledge of the timing of sulci appearance, myelination and changes in ventricular size. With advanced gestation, fetal organs as lungs and kidneys show significant changes in volume and T2-signal. Through a systematic approach, the normal anatomy of the developing fetus is shown to contrast with a wide spectrum of fetal disorders. The abnormalities displayed are graded in severity from simple common lesions to more complex rare cases. Complete fetal MRI is fulfilled by careful evaluation of the placenta, umbilical cord and amniotic cavity. Accurate interpretation of fetal MRI can provide valuable information that helps prenatal counseling, facilitate management decisions, guide therapy, and support research studies.

  19. Study of the development of uteroplacental and fetal feline circulation by triplex Doppler.

    Science.gov (United States)

    Pereira, Barbara Sucupira; Pinto, José Nicodemos; Freire, Luma Morena Passos; Campello, Cláudio Cabral; Domingues, Sheyla Farhayldes Souza; da Silva, Lucia Daniel Machado

    2012-03-15

    The objective was to evaluate blood flow in fetal and maternal vessels by Triplex Doppler and its association with development of blood vessels during gestation in the domestic cat. Ten queens were examined weekly from 14 to 63 d after mating. Peak systolic velocity (PSV), end diastolic velocity (EDV), resistance index (RI) and pulsatility index (PI) of uteroplacental, aorta and umbilical fetal arteries and caudal vena cava of the fetus were evaluated. Throughout pregnancy, there was an increase in PSV and EDV in the aorta and umbilical arteries. In the caudal vena cava, there was an increase in PSV, whereas the EDV was constant, with a significant increase on Day 63. Peak systolic velocity and EDV of the uteroplacental artery reduced significantly on Day 63. Resistance index of the umbilical artery progressively decreased. In the aorta, this reduction was detected only on Day 42, with no defined pattern in the caudal vena cava and uteroplacental artery. Pulsatility index of the aorta varied. Although pulsatility increased in the caudal vena cava on Day 35 and remained elevated, pulsatility was significantly reduced in the umbilical artery by Day 63. The pulsatility index of the uteroplacental artery was constant (increased only on Day 63). Triplex Doppler evaluation could be a useful adjunct for prenatal care of pregnant queens, including assessment of vascular gestational development and prediction of gestational age.

  20. Physical principles for developing a synthetic lung surfactant

    Energy Technology Data Exchange (ETDEWEB)

    Jaehnig, F. (Max-Planck-Institut fuer Biologie, Tuebingen (Germany, F.R.)); Obladen, M. (Tuebingen Univ. (Germany, F.R.). Kinderklinik)

    1984-01-01

    The physical principles for developing a synthetic lung surfactant to treat the respiratory distress syndrome are discussed. Requirements for the lipid composition and preparation of the synthetic surfactant are detailed, leading to the conclusion that a suspension of large unilamellar vesicles consisting of dipalmitoylphosphatidylcholine and a small amount of unsaturated lipid is a promising choice.

  1. Distinct Genetic Networks Orchestrate the Emergence of Specific Waves of Fetal and Adult B-1 and B-2 Development.

    Science.gov (United States)

    Montecino-Rodriguez, Encarnacion; Fice, Michael; Casero, David; Berent-Maoz, Beata; Barber, Chad L; Dorshkind, Kenneth

    2016-09-20

    B cell development is often depicted as a linear process initiating in the fetus and continuing postnatally. Using a PU.1 hypomorphic mouse model, we found that B-1 and B-2 lymphopoiesis occurred in distinct fetal and adult waves differentially dependent on the Sfpi1 14 kB upstream regulatory element. The initial wave of fetal B-1 development was absent in PU.1 hypomorphic mice, while subsequent fetal and adult waves emerged. In contrast, B-2 lymphopoiesis occurred in distinct fetal and adult waves. Whole-transcriptome profiling of fetal and adult B cell progenitors supported the existence of three waves of B-1 and two waves of B-2 development and revealed that the network of transcription factors governing B lineage specification and commitment was highly divergent between B-1 and B-2 progenitors. These findings support the view that the B-1 and B-2 lineages are distinct and provide a genetic basis for layering of immune system development.

  2. 三维超声测量胎儿肺容积的准确性研究%Accuracy of Fetal Lung Volume Assessed by Three-dimensional Sonography

    Institute of Scientific and Technical Information of China (English)

    张波; 杨太珠

    2011-01-01

    Objective To assess the value of 3D ultrasound in fetal lung volume measurement using VOCAL technique,and to determine its accuracy and reproducibility.Methods Fetal lung volumes were measured using VOCAL technique in 14 cases with pulmonary hypoplasia and in 17 controls 1-3 days before termination.Postmortem autopsy was conducted within 6 hours after labor and the lung volume was achieved by water displacement.Results The correlation between measured volume and postmortem examination was significant,with correlation coefficient 0.80 in pathological cases and 0.96 in controls.The mean relative error, bias, 95% limits of agreement were, respectively,-2.31%, -0.19 cm3 and ( - 3.59-3.20) cm3 in cases with pulmonary hypoplasia and - 1.06%, - 0.37 cm3 and (-6.12-5.38) cm3 in controls.Good intraobserver and interobserver reproducibility were achieved, both in pathological cases and in controls.Conclusions Prenatal 3D ultrasound can estimate accurately fetal lung volume using VOCAL technique, both in normal and pathological situation ,which conduces to evaluation of its physiological development.%目的 探讨三维超声VOCAL技术在胎儿肺容积测量中的应用价值,并评价其准确性及重复性.方法 收集拟引产胎儿31例,其中病理组(有肺发育不良高危因素)14例,对照组(无肺发育不良高危因素)17例.引产前1~3 d应用VOCAL法分别测得胎儿左、右肺容积值,相加得到总肺容积,引产后6 h内对胎儿进行病理检查,应用水置换法得到其实际总肺容积.结果 (1)三维超声测值与病理检查结果间有良好的相关性,病理组与对照组的相关系数(r)分别为0.80及0.96(P均<0.01);(2)三维超声测量病理组胎肺容积的平均相对误差,偏倚及95%一致性界限分别为-2.31%、-0.19 cm3及(-3.59~3.20)cm3,而对照组分别为-1.06%、-0.37 cm3及(-6.12~5.38)cm3;(3)三维超声对病理组及对照组胎肺容积进行测量时的操作者内及操作者间变异较小,

  3. MicroRNA-26a modulates transforming growth factor beta-1-induced proliferation in human fetal lung fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xiaoou [Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China); Department of Respiratory Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China); Liu, Lian [Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China); Shen, Yongchun; Wang, Tao; Chen, Lei; Xu, Dan [Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China); Department of Respiratory Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China); Wen, Fuqiang, E-mail: wenfuqiang.scu@gmail.com [Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China); Department of Respiratory Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China)

    2014-11-28

    Highlights: • Endogenous miR-26a inhibits TGF-beta 1 induced proliferation of lung fibroblasts. • miR-26a induces G1 arrest through directly targeting 3′-UTR of CCND2. • TGF indispensable receptor, TGF-beta R I, is regulated by miR-26a. • miR-26a acts through inhibiting TGF-beta 2 feedback loop to reduce TGF-beta 1. • Collagen type I and connective tissue growth factor are suppressed by miR-26a. - Abstract: MicroRNA-26a is a newly discovered microRNA that has a strong anti-tumorigenic capacity and is capable of suppressing cell proliferation and activating tumor-specific apoptosis. However, whether miR-26a can inhibit the over-growth of lung fibroblasts remains unclear. The relationship between miR-26a and lung fibrosis was explored in the current study. We first investigated the effect of miR-26a on the proliferative activity of human lung fibroblasts with or without TGF-beta1 treatment. We found that the inhibition of endogenous miR-26a promoted proliferation and restoration of mature miR-26a inhibited the proliferation of human lung fibroblasts. We also examined that miR-26a can block the G1/S phase transition via directly targeting 3′-UTR of CCND2, degrading mRNA and decreasing protein expression of Cyclin D2. Furthermore, we showed that miR-26a mediated a TGF-beta 2-TGF-beta 1 feedback loop and inhibited TGF-beta R I activation. In addition, the overexpression of miR-26a also significantly suppressed the TGF-beta 1-interacting-CTGF–collagen fibrotic pathway. In summary, our studies indicated an essential role of miR-26a in the anti-fibrotic mechanism in TGF-beta1-induced proliferation in human lung fibroblasts, by directly targeting Cyclin D2, regulating TGF-beta R I as well as TGF-beta 2, and suggested the therapeutic potential of miR-26a in ameliorating lung fibrosis.

  4. Canonical Sonic Hedgehog Signaling in Early Lung Development

    Directory of Open Access Journals (Sweden)

    Hugo Fernandes-Silva

    2017-03-01

    Full Text Available The canonical hedgehog (HH signaling pathway is of major importance during embryonic development. HH is a key regulatory morphogen of numerous cellular processes, namely, cell growth and survival, differentiation, migration, and tissue polarity. Overall, it is able to trigger tissue-specific responses that, ultimately, contribute to the formation of a fully functional organism. Of all three HH proteins, Sonic Hedgehog (SHH plays an essential role during lung development. In fact, abnormal levels of this secreted protein lead to severe foregut defects and lung hypoplasia. Canonical SHH signal transduction relies on the presence of transmembrane receptors, such as Patched1 and Smoothened, accessory proteins, as Hedgehog-interacting protein 1, and intracellular effector proteins, like GLI transcription factors. Altogether, this complex signaling machinery contributes to conveying SHH response. Pulmonary morphogenesis is deeply dependent on SHH and on its molecular interactions with other signaling pathways. In this review, the role of SHH in early stages of lung development, specifically in lung specification, primary bud formation, and branching morphogenesis is thoroughly reviewed.

  5. Toxicity of bryostatin-1 on the embryo-fetal development of Sprague-Dawley rats.

    Science.gov (United States)

    Jiangbo, Zhu; Xuying, Wan; Yuping, Zhu; Xili, Ma; Yiwen, Zheng; Tianbao, Zhang

    2010-06-01

    Bryostatin-1, a highly oxygenated marine macrolide with a unique polyacetate backbone isolated from the marine animal Bugula neritina (Linnaeus), is now being developed as an anti-cancer drug for treating malignancy. In the present study, developmental toxicity of bryostatin-1 was evaluated in Sprague-Dawley rats. Bryostatin-1 was intravenously administered to rats on gestation days 6-15 at 4.0, 8.0, and 16.0 microg/kg on a daily basis. Then the reproductive parameters were determined in animals, and fetuses were examined for external, visceral, and skeletal malformations. The total weight gains were significantly different in animals between the control group and 8.0 and 16.0 microg/kg bryostatin-1 groups during and after treatment. The resorption and death fetus rates were significantly different between the bryostatin-1 group (16 microg/kg) and the control group. The fetal weight and fetal crown-rump length in the bryostatin-1 groups were significantly lower than that in the control group. Our results indicated that maternal toxicity occurred when the dose of bryostatin-1 was at 8.0 microg/kg, embryotoxicity at 16.0 microg/kg, and fetotoxicity at 4.0 microg/kg; but bryostatin-1 showed no teratogenic effect in rats. In light of our findings, bryostatin-1 should be used with caution in pregnant women with cancer, if they would like to continue the pregnancy.

  6. Human fetal liver stromal cells expressing erythropoietin promote hematopoietic development from human embryonic stem cells.

    Science.gov (United States)

    Yang, Chao; Ji, Lei; Yue, Wen; Shi, Shuang-Shuang; Wang, Ruo-Yong; Li, Yan-Hua; Xie, Xiao-Yan; Xi, Jia-Fei; He, Li-Juan; Nan, Xue; Pei, Xue-Tao

    2012-02-01

    Blood cells transfusion and hematopoietic stem cells (HSCs) transplantation are important methods for cell therapy. They are widely used in the treatment of incurable hematological disorder, infectious diseases, genetic diseases, and immunologic deficiency. However, their availability is limited by quantity, capacity of proliferation and the risk of blood transfusion complications. Recently, human embryonic stem cells (hESCs) have been shown to be an alternative resource for the generation of hematopoietic cells. In the current study, we describe a novel method for the efficient production of hematopoietic cells from hESCs. The stable human fetal liver stromal cell lines (hFLSCs) expressing erythropoietin (EPO) were established using the lentiviral system. We observed that the supernatant from the EPO transfected hFLSCs could induce the hESCs differentiation into hematopoietic cells, especially erythroid cells. They not only expressed fetal and embryonic globins but also expressed the adult-globin chain on further maturation. In addition, these hESCs-derived erythroid cells possess oxygen-transporting capacity, which indicated hESCs could generate terminally mature progenies. This should be useful for ultimately developing an animal-free culture system to generate large numbers of erythroid cells from hESCs and provide an experimental model to study early human erythropoiesis.

  7. Development of bactericidal capacity and phagocytosis-associated metabolism of fetal pig leukocytes.

    Science.gov (United States)

    Holmes, B; Day, N; Haseman, J; Good, R A

    1972-02-01

    Evidence that the bactericidal ability and the stimulated oxidative metabolism of leukocytes appear in parallel during fetal development of the Minnesota Miniature pig has been obtained by application of the techniques applied to studies of human cells. It was demonstrated that leukocytes from 87- to 90-day fetuses were fully capable of ingesting Staphylococcus aureus but greatly diminished in bactericidal capacity as compared to leukocytes of older fetuses and adults. Although resting levels of oxygen consumption and hexose monophosphate pathway activity of leukocytes from the younger fetuses compared well with those of leukocytes from older animals, the phagocytosis-stimulated increments of metabolism were much less at 87 to 90 days of gestation than at later developmental stages. Both bactericidal capacity and increased metabolism of leukocytes reach adult levels by 100 days of gestation (normal gestation period of 115 to 120 days). Acrylamide gels stained for reduced nicotinamide adenine dinucleotide (NADH) and NADH phosphate (NADPH) diaphorase activity after disc electrophoresis of leukocyte extracts revealed normal mobility and intensity of NADH diaphorase bands. Three NADPH diaphorase bands were present in adult leukocyte extracts. Only the fast-migrating NADPH diaphorase band of 87- to 90-day cells stained with decreased intensity. This "deficiency" was no longer present at the later fetal period. The fast-migrating NADPH diaphorase band may represent an electron transfer protein which functions in cyanide-insensitive respiration of the leukocytes of the pig.

  8. [Two cases of acute promyelocytic leukemia in pregnancy and the effect of anthracyclines on fetal development].

    Science.gov (United States)

    Takatsuki, H; Abe, Y; Goto, T; Sadamura, S; Taguchi, F; Muta, K; Miyoshi, T; Katsuno, M; Umemura, T; Nishimura, J

    1992-11-01

    Two patients with acute promyelocytic leukemia (APL) in 2nd and 3rd trimester of pregnancy are reported on. Case 1: 38-year-old female consulted our hospital because of bleeding tendency and pancytopenia in April, 1988. She was diagnosed as having APL with disseminated intravascular coagulopathy (DIC) and was found to be in the 14th week of gestation. Combined chemotherapy (BHAC-DMP) including the total dose (440 mg) of daunorubicin (DNR) resulted in intrauterine fetal death at 19 weeks of gestation. The fetus was severely anemic and the bone marrow was hypoplastic. Case 2: A 27-year-old female was diagnosed as having APL with DIC at 29 weeks of gestation. BHAC-DMP including 440 mg DNR achieved complete remission. At 35 weeks of gestation, she delivered a normal infant by Caesarean section. The child had normal hematological findings and showed normal growth. Both cases developed APL accompanied by DIC during pregnancy and were treated with a similar regimen including high dose of anthracyclines. Case 2 treated in the late period of gestation delivered a normal infant, while fetal death resulted in case 1, treated in the early period of gestation. We reviewed the literature regarding chemotherapy using anthracyclines during pregnancy.

  9. The expression of thyroid hormone transporters in the human fetal cerebral cortex during early development and in N-Tera-2 neurodifferentiation

    OpenAIRE

    Chan, S.Y.; Martín-Santos, A; Loubière, L S; González, A. M.; Stieger, B.; LOGAN, A.; McCabe, C. J.; Franklyn, J.A.; Kilby, M. D.

    2011-01-01

    Associations of neurological impairment with mutations in the thyroid hormone (TH) transporter, MCT8, and with maternal hypothyroxinaemia, suggest that THs are crucial for human fetal brain development. It has been postulated that TH transporters regulate the cellular supply of THs within the fetal brain during development. This study describes the expression of TH transporters in the human fetal cerebral cortex (7–20 weeks gestation) and during retinoic acid induced neurodifferentiation of t...

  10. Embryonic alcohol exposure: Towards the development of a zebrafish model of fetal alcohol spectrum disorders.

    Science.gov (United States)

    Gerlai, Robert

    2015-11-01

    Fetal alcohol spectrum disorder (FASD) is a devastating disease of the brain caused by exposure to alcohol during prenatal development. Its prevalence exceeds 1%. The majority of FASD cases represent the milder forms of the disease which often remain undiagnosed, and even when diagnosed treatment options for the patient are limited due to lack of information about the mechanisms that underlie the disease. The zebrafish has been proposed as a model organism for exploring the mechanisms of FASD. Our laboratory has been studying the effects of low doses of alcohol during embryonic development in the zebrafish. This review discusses the methods of alcohol exposure, its effects on behavioral performance including social behavior and learning, and the potential underlying biological mechanisms in zebrafish. It is based upon a recent keynote address delivered by the author, and it focuses on findings obtained mainly in his own laboratory. It paints a promising future of this small vertebrate in FASD research.

  11. Toxic effects of maternal zearalenone exposure on uterine capacity and fetal development in gestation rats.

    Science.gov (United States)

    Zhang, Yuanyuan; Jia, Zhiqiang; Yin, Shutong; Shan, Anshan; Gao, Rui; Qu, Zhe; Liu, Min; Nie, Shaoping

    2014-06-01

    The objectives of this study were to determine the effects of high-dose and early gestational exposure to zearalenone (ZEN) in female Sprague-Dawley (SD) rats, to correlate the maternal uterus with the fetus, and to explore the development and malformation of fetuses. Pregnant female SD rats were fed diets containing 0.3, 48.5, 97.6, or 146.0 mg/kg ZEN on gestational days (GDs) 0 through 7. All the females survived until GD 20, at which point a cesarean section was performed to harvest the organs, blood, and fetuses. The results indicated that exposure to ZEN during early gestation can impact the maternal reproductive capability. Delayed fetal development was directly linked to maternal toxicity. The toxic effects of ZEN caused early deaths more frequently than late deaths, and the deleterious effects lasted through the end of pregnancy.

  12. Repercussions of mild diabetes on pregnancy in Wistar rats and on the fetal development

    Directory of Open Access Journals (Sweden)

    Saito Felipe H

    2010-04-01

    Full Text Available Abstract Background Experimental models are necessary to elucidate diabetes pathophysiological mechanisms not yet understood in humans. Objective: To evaluate the repercussions of the mild diabetes, considering two methodologies, on the pregnancy of Wistar rats and on the development of their offspring. Methods In the 1st induction, female offspring were distributed into two experimental groups: Group streptozotocin (STZ, n = 67: received the β-cytotoxic agent (100 mg STZ/kg body weight - sc on the 1st day of the life; and Non-diabetic Group (ND, n = 14: received the vehicle in a similar time period. In the adult life, the animals were mated. After a positive diagnosis of pregnancy (0, female rats from group STZ presenting with lower glycemia than 120 mg/dL received more 20 mg STZ/kg (ip at day 7 of pregnancy (2nd induction. The female rats with glycemia higher than 120 mg/dL were discarded because they reproduced results already found in the literature. In the mornings of days 0, 7, 14 and 21 of the pregnancy glycemia was determined. At day 21 of pregnancy (at term, the female rats were anesthetized and killed for maternal reproductive performance and fetal development analysis. The data were analyzed using Student-Newman-Keuls, Chi-square and Zero-inflated Poisson (ZIP Tests (p Results STZ rats presented increased rates of pre (STZ = 22.0%; ND = 5.1% and post-implantation losses (STZ = 26.1%; ND = 5.7%, reduced rates of fetuses with appropriate weight for gestational age (STZ = 66%; ND = 93% and reduced degree of development (ossification sites. Conclusion Mild diabetes led a negative impact on maternal reproductive performance and caused intrauterine growth restriction and impaired fetal development.

  13. Mapping primary gyrogenesis during fetal development in primate brains: high-resolution in utero structural MRI study of fetal brain development in pregnant baboons

    Directory of Open Access Journals (Sweden)

    Peter Kochunov

    2010-05-01

    Full Text Available The global and regional changes in the fetal cerebral cortex in primates were mapped during primary gyrification (PG; weeks 17-25 of 26 weeks total gestation. Studying pregnant baboons using high-resolution MRI in utero, measurements included cerebral volume, cortical surface area, gyrification index and length and depth of ten primary cortical sulci. Seven normally developing fetuses were imaged in two animals longitudinally and sequentially. We compared these results to those on PG that from the ferret studies and analyzed them in the context of our recent studies of phylogenetics of cerebral gyrification. We observed that in both primates and non-primates, the cerebrum undergoes a very rapid transformation into the gyrencephalic state, subsequently accompanied by an accelerated growth in brain volume and cortical surface area. However, PG trends in baboons exhibited some critical differences from those observed in ferrets. For example, in baboons, the growth along the long (length axis of cortical sulci was unrelated to the growth along the short (depth axis and far outpaced it. Additionally, the correlation between the rate of growth along the short sulcal axis and heritability of sulcal depth was negative and approached significance (r=-0.60;p<.10, while the same trend for long axis was positive and not significant (p=0.3;p=0.40. These findings, in an animal that shares a highly orchestrated pattern of PG with humans, suggest that ontogenic processes that influence changes in sulcal length and depth are diverse and possibly driven by different factors in primates than in non-primates.

  14. Maternal smoking and the retinoid pathway in the developing lung

    Directory of Open Access Journals (Sweden)

    Manoli Sara E

    2012-06-01

    Full Text Available Abstract Background Maternal smoking is a risk factor for pediatric lung disease, including asthma. Animal models suggest that maternal smoking causes defective alveolarization in the offspring. Retinoic acid signaling modulates both lung development and postnatal immune function. Thus, abnormalities in this pathway could mediate maternal smoking effects. We tested whether maternal smoking disrupts retinoic acid pathway expression and functioning in a murine model. Methods Female C57Bl/6 mice with/without mainstream cigarette smoke exposure (3 research cigarettes a day, 5 days a week were mated to nonsmoking males. Cigarette smoke exposure continued throughout the pregnancy and after parturition. Lung tissue from the offspring was examined by mean linear intercept analysis and by quantitative PCR. Cell culture experiments using the type II cell-like cell line, A549, tested whether lipid-soluble cigarette smoke components affected binding and activation of retinoic acid response elements in vitro. Results Compared to tobacco-naïve mice, juvenile mice with tobacco toxin exposure had significantly (P  Conclusions A murine model of maternal cigarette smoking causes abnormal alveolarization in association with altered retinoic acid pathway element expression in the offspring. An in vitro cell culture model shows that lipid-soluble components of cigarette smoke decrease retinoic acid response element activation. It is feasible that disruption of retinoic acid signaling contributes to the pediatric lung dysfunction caused by maternal smoking.

  15. Air pollution effects on fetal and child development: a cohort comparison in China.

    Science.gov (United States)

    Tang, Deliang; Li, Ting Yu; Chow, Judith C; Kulkarni, Sanasi U; Watson, John G; Ho, Steven Sai Hang; Quan, Zhang Y; Qu, L R; Perera, Frederica

    2014-02-01

    In Tongliang, China, a coal-fired power plant was the major pollution source until its shutdown in 2004. We enrolled two cohorts of nonsmoking women and their newborns before and after the shutdown to examine the relationship between prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) and fetal and child growth and development. PAHs were used to measure exposure to air pollution generated by the power plant. Using PAH-DNA adduct levels as biomarkers for the biologically effective dose of PAH exposure, we examined whether PAH-DNA adduct levels were associated with birth outcome, growth rate, and neurodevelopment. Head circumference was greater in children of the second cohort, compared with the first (p = 0.001), consistent with significantly reduced levels of cord blood PAH-DNA adducts in cohort II (p < 0.001) and reduced levels of ambient PAHs (p = 0.01).

  16. Ontogenic development of corticotrophs in fetal buffalo (Bubalus bubalis pituitary gland

    Directory of Open Access Journals (Sweden)

    M. A. Sandhu

    2014-01-01

    Full Text Available To evaluate the subpopulation of corticotrophs in developing buffalo (Bubalus bubalis fetus, recovered pituitary glands (n=6 per group from late first, second and third gestational female buffalo dams. The corticotrophs were identified by using specific antibodies against proopiomelanocortin (POMC and adrenocorticotrophic hormone (ACTH through immunohistochemistry. There was a significant (P≤0.05 increase of immunoreactive (ir ir-ACTH cells during late 2nd trimester while, ir-POMC cells were more (P≤0.05 at late 3rd trimester of gestation as compared to other age groups. The quantity of co-localized cells for POMC and ACTH was significantly (P≤0.05 greater at the end of 1st gestation rather than 2nd and 3rd gestational fetal adenohypophyseal cells. This study is the first to demonstrate co-localization of POMC+ACTH and the affect of gestational age on the expression of these cells in buffalo fetus adenohypophysis.

  17. Development of the Korean Paternal-Fetal Attachment Scale (K-PAFAS).

    Science.gov (United States)

    Noh, Nan Iee; Yeom, Hye-Ah

    2017-06-01

    This study is a methodological study aimed to develop the Korean Paternal-Fetal Attachment Scale (K-PAFAS) to measure the level of attachment between the father and the expected baby, and to examine its validity and reliability. The K-PAFAS was developed in four steps. The first step involved derivation of the initial items through review of the literature and in-depth interviews with 10 expectant fathers. The second step was the process of expert panel review, examining content validity for the initial items. In the third step, items were examined for their usability through a preliminary survey with 30 expectant fathers. As the last step, the final K-PAFAS was applied to 200 participants and examined for its psychometric profile. K-PAFAS consisted of 20 items, and used a 5-point Likert scale with the total score ranging from 20 points to 100 points. A higher score indicated a higher level of attachment between the father and his unborn child. The K-PAFAS was composed of four factors. The K-PAFAS demonstrated satisfactory criterion validity, which was supported by its significant correlations with the Paternal Antenatal Attachment Scale, the Korean Dyadic Adjustment Scale, and the Center for Epidemiological Studies-Depression Scale. The Cronbach α of the K-PAFAS was .89. In test-retest reliability, the K-PAFAS showed a correlation coefficient of .91. The K-PAFAS demonstrated initial validity and reliability. It was short, and relatively easy for use in evaluating the degree of paternal-fetal attachment in the antenatal management stage. Copyright © 2017. Published by Elsevier B.V.

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

    Directory of Open Access Journals (Sweden)

    Cornelle W Noorlander

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

  19. Fetal development and risk of cardiovascular diseases and diabetes type 2 in adult life.

    Science.gov (United States)

    Szostak-Węgierek, Dorota; Szamotulska, Katarzyna

    2011-01-01

    The fetal origin hypothesis of adult cardiovascular diseases, type 2 diabetes, hypertension and dyslipidemia in persons born with low birthweight, independently of their extrauterine risk factors, has been well established in the last decade of the twentieth century. However, mechanisms responsible for this relationship are still under investigation. Insulin resistance resulting from the restriction of intrauterine development of skeletal muscles and other organs is considered as the most important cause of metabolic disturbances and their cardiovascular complications in adult subjects born with intrauterine growth retardation (IUGR). Decline of insulin secretion, overactivation of the hypothalamo-pituitary-adrenal axis, reduced glucose uptake in the liver and raised lipid oxidation in the muscles may also explain this association. On the other hand, abnormal vascular development , increased activity of the sympathetic nervous system, defective endothelial function and/or impaired renal function in growth restricted newborns may contribute to hypertension in their later life. With respect to maternal conditions and life-style factors that may increase cardiovascular risk in adult offspring born with IUGR, the most consistent results concern pregnancy induced hypertension, preeclampsia, undernutrition, smoking during pregnancy, hypercholesterolemia, inflammation and/or enhanced glucocorticoid secretion. Macrosomia of the newborn, a frequent sequel to maternal diabetes and/or obesity, also increases the risk of diabetes and cardiovascular diseases in adulthood. Maternal overnutrition, and particularly high fat and sugar intake, seem to play a key role in fetal programming of cardiovascular risk in subjects born with macrosomia. Epigenetic imprinting underlies the described pathomechanisms. The presented associations are illustrated, among others, with the results of studies performed by the authors of this review.

  20. 78 FR 33851 - Lung Cancer Patient-Focused Drug Development; Public Meeting

    Science.gov (United States)

    2013-06-05

    ... No. FDA-2013-N-0596] Lung Cancer Patient-Focused Drug Development; Public Meeting AGENCY: Food and... Patient-Focused Drug Development for lung cancer. Patient-Focused Drug Development is part of FDA's... cancer on daily life as well as the available therapies for lung cancer. DATES: The public meeting...

  1. Sonographic assessment of normal and abnormal fetal development; early and late aspects

    NARCIS (Netherlands)

    N.S. den Hollander (Nicolette)

    2002-01-01

    textabstractThis thesis consists of two parts. The first part deals with an increasingly important area of first and early second trimester (<14 weeks) normal and abnmmal fetal sonoanatomy and its validity and impact in the early diagnosis of fetal anomalies in a high-risk population. The second par

  2. Phosphatidylglycerol determination in the amniotic fluid from a PAD placed over the vulva: a method for diagnosis of fetal lung maturity in cases of premature ruptured membranes.

    Science.gov (United States)

    Estol, P C; Poseiro, J J; Schwarcz, R

    1992-01-01

    Four hundred and forty seven pregnant women with ruptured membranes, were prospectively studied in order to assess the diagnostic capacity of Phosphatidylglycerol (PhG) determination in amniotic fluid recovered from vulval pads in the diagnosis of Hyaline Membrane Disease (HMD). The identification of PhG was performed using one dimensional silica gel thin layer chromatography. The sensitivity of PhG determination in the diagnosis of HMD in newborns of the total population was found to be 88.2%, with a specificity of 76.9%. In the study population, the incidence of HMD was 7.6%, the negative predictive value was 98.8% and, the positive predictive value was 24.0%. When the 265 newborns of the gestational age group of less than or equal to 34 weeks is considered, we observed an incidence of HMD of 12.1%. The diagnostic capacity of PhG in this group was shown by a sensitivity of 87.5%, a specificity of 76.4%, a positive predictive value of 33.7% and a negative predictive value of 97.8%. This method of assessment of fetal lung maturity has a diagnostic capability similar to that described by other authors, who used amniotic fluid obtained vaginally or transabdominally. The procedure described here of amniotic fluid collection is non-invasive, harmless to the mother and fetus and simple to perform. The characteristics of this method, allow serial studies of the amniotic fluid to be carried out.

  3. [The phenol turbidity test for measurement of pulmonary surfactants in amniotic fluid--rapid test for fetal lung maturity (author's transl)].

    Science.gov (United States)

    Tatsumi, H; Shimada, N; Kuramoto, R; Mochizuki, Y; Nishizima, M; Arai, M; Osanai, K; Ishihara, K; Goso, K; Hotta, K

    1981-05-01

    A simple and sensitive procedure for the quantitative estimation of pulmonary surfactants in the amniotic fluid is described. The method is based on the formation of turbidity from the amniotic fluid surfactants with phenol. Amniotic fluid drawn through an intrauterine catheter was centrifuged at 2000 rpm for 5 min. One ml of 5% aqueous phenol solution was added to 1.0 ml of the diluted supernatant. Control solution was prepared by addition of 1.0 ml of distilled water to the supernatant, instead of phenol solution. The turbidity was measured spectrophotometrically against control at 340 nm 5 to 10 min after agitation on a Vortex mixer for 5 sec. The turbidity obtained from amniotic fluid with phenol was proportional to the increase in total phospholipids in the fluid measured enzymatically. Moreover, only lecithin in the phospholipids was related to the turbidity formation. Sphyngomyelin, lysolecithin, phosphatidylethanolamin did not produce any turbidity with phenol. The spectrophotometric reading of 87 cases (31-41 weeks) was ranged at 0.18-3.52. Four cases with lower value (0.40) showed neonatal respiratory problem. The phenol turbidity test is more useful for the detection of fetal lung maturity comparing with the generally used shake test.

  4. Bovine Herpesvirus 1 Protein bICP0 Represses the Transcription of bISG15 in Fetal Bovine Lung Cells

    Institute of Scientific and Technical Information of China (English)

    Chang Liu; Xiao-hong Kong; Wen-tao Qiao; Yun-qi Geng

    2011-01-01

    The ubiquitin-like modifier bISG15 is an antiviral protein found in fetal bovine lung (FBL) cells.Bovine Herpesvirus 1(BHV-1),which is a viral pathogen of cattle,can infect FBL cells and induce cytopathic effects.Real-time PCR assays showed that BHV- 1 's infection could repress the basal or inducible transcription of bISG15 in FBL cells.It demonstrates that this repression effect depends on BHV-1 viral infection and new protein synthesis.Our previous work showed that bIRF-3 was the key factor in the stimulation of bISG 15 in FBL cells,so the effect of BHV-1 viral protein on bIRF-3 activating the promoter of bISG15 was confirmed.The luciferase assay showed the BHV-1 viral protein bICP0 inhibited the activation of bISG15 promoter stimulated by bIRF-3.Taken together,our work suggested that BHV-I had some molecular mechanism to resist the cellular bISG15'santiviral functions.

  5. Comparative assessments of the effects of alcohol exposure on fetal brain development using optical coherence tomography and ultrasound imaging

    Science.gov (United States)

    Sudheendran, Narendran; Bake, Shameena; Miranda, Rajesh C.; Larin, Kirill V.

    2013-02-01

    The developing fetal brain is vulnerable to a variety of environmental agents including maternal ethanol consumption. Preclinical studies on the development and amelioration of fetal teratology would be significantly facilitated by the application of high resolution imaging technologies like optical coherence tomography (OCT) and high-frequency ultrasound (US). This study investigates the ability of these imaging technologies to measure the effects of maternal ethanol exposure on brain development, ex vivo, in fetal mice. Pregnant mice at gestational day 12.5 were administered ethanol (3 g/Kg b.wt.) or water by intragastric gavage, twice daily for three consecutive days. On gestational day 14.5, fetuses were collected and imaged. Three-dimensional images of the mice fetus brains were obtained by OCT and high-resolution US, and the volumes of the left and right ventricles of the brain were measured. Ethanol-exposed fetuses exhibited a statistically significant, 2-fold increase in average left and right ventricular volumes compared with the ventricular volume of control fetuses, with OCT-derived measures of 0.38 and 0.18 mm3, respectively, whereas the boundaries of the fetal mouse lateral ventricles were not clearly definable with US imaging. Our results indicate that OCT is a useful technology for assessing ventriculomegaly accompanying alcohol-induced developmental delay. This study clearly demonstrated advantages of using OCT for quantitative assessment of embryonic development compared with US imaging.

  6. Development of a preparation and staining method for fetal erythroblasts in maternal blood : Simultaneous immunocytochemical staining and FISH analysis

    NARCIS (Netherlands)

    Oosterwijk, JC; Mesker, WE; Ouwerkerk-van Velzen, MCM; Knepfle, CFHM; Wiesmeijer, KC; van den Burg, MJM; Beverstock, GC; Bernini, LF; van Ommen, Gert-Jan B; Kanhai, HHH; Tanke, HJ

    1998-01-01

    In order to detect fetal nucleated red blood cells (NRBCs) in maternal blood, a protocol was developed which aimed at producing a reliable staining method for combined immunocytochemical and FISH analysis. The technique had to be suitable for eventual automated screening of slides. Chorionic villi w

  7. Variability in Classroom Social Communication: Performance of Children with Fetal Alcohol Spectrum Disorders and Typically Developing Peers

    Science.gov (United States)

    Kjellmer, Liselotte; Olswang, Lesley B.

    2013-01-01

    Purpose: In this study, the authors examined how variability in classroom social communication performance differed between children with fetal alcohol spectrum disorders (FASD) and pair-matched, typically developing peers. Method: Twelve pairs of children were observed in their classrooms, 40 min per day (20 min per child) for 4 days over a…

  8. PAH-DNA adducts in cord blood and fetal and child development in a Chinese cohort

    Energy Technology Data Exchange (ETDEWEB)

    Tang, D.L.; Li, T.Y.; Liu, J.J.; Chen, Y.H.; Qu, L.R.; Perera, F. [Columbia University, New York, NY (United States). Dept. for Environmental Health Science

    2006-08-15

    Polycyclic aromatic hydrocarbons (PAHs) are an important class of toxic pollutants released by fossil fuel combustion. Other pollutants include metals and particulate matter. PAH-DNA adducts, or benzo(a)pyrene (BaP) adducts as their proxy, provide a chemical-specific measure of individual biologically effective doses that have been associated with increased risk of cancer and adverse birth outcomes. In the present study we examined the relationship between prenatal PAH exposure and fetal and child growth and development in Tongliang, China, where a seasonally operated coal-fired power plant was the major pollution source. In a cohort of 150 nonsmoking women and their newborns enrolled between 4 March 2002 and 19 June 2002, BaP-DNA adducts were measured in maternal and umbilical cord blood obtained at delivery. High PAH-DNA adduct levels (above the median of detectable adduct level) were associated with decreased birth head circumference (p = 0.057) and reduced children's weight at 18 months, 24 months, and 30 months of age (p {lt} 0.05), after controlling for potential confounders. In addition, in separate models, longer duration of prenatal exposure was associated with reduced birth length (p = 0.033) and reduced children's height at 18 (p = 0.001), 24 (p {lt} 0.001), and 30 months of age (p {lt} 0.001). The findings suggest that exposure to elevated levels of PAHS, with the Tongliang power plant being a significant source, is associated with reduced fetal and child growth in this population.

  9. Fetal functional imaging portrays heterogeneous development of emerging human brain networks.

    Science.gov (United States)

    Jakab, András; Schwartz, Ernst; Kasprian, Gregor; Gruber, Gerlinde M; Prayer, Daniela; Schöpf, Veronika; Langs, Georg

    2014-01-01

    The functional connectivity architecture of the adult human brain enables complex cognitive processes, and exhibits a remarkably complex structure shared across individuals. We are only beginning to understand its heterogeneous structure, ranging from a strongly hierarchical organization in sensorimotor areas to widely distributed networks in areas such as the parieto-frontal cortex. Our study relied on the functional magnetic resonance imaging (fMRI) data of 32 fetuses with no detectable morphological abnormalities. After adapting functional magnetic resonance acquisition, motion correction, and nuisance signal reduction procedures of resting-state functional data analysis to fetuses, we extracted neural activity information for major cortical and subcortical structures. Resting fMRI networks were observed for increasing regional functional connectivity from 21st to 38th gestational weeks (GWs) with a network-based statistical inference approach. The overall connectivity network, short range, and interhemispheric connections showed sigmoid expansion curve peaking at the 26-29 GW. In contrast, long-range connections exhibited linear increase with no periods of peaking development. Region-specific increase of functional signal synchrony followed a sequence of occipital (peak: 24.8 GW), temporal (peak: 26 GW), frontal (peak: 26.4 GW), and parietal expansion (peak: 27.5 GW). We successfully adapted functional neuroimaging and image post-processing approaches to correlate macroscopical scale activations in the fetal brain with gestational age. This in vivo study reflects the fact that the mid-fetal period hosts events that cause the architecture of the brain circuitry to mature, which presumably manifests in increasing strength of intra- and interhemispheric functional macro connectivity.

  10. Fetal functional imaging portrays heterogeneous development of emerging human brain networks

    Science.gov (United States)

    Jakab, András; Schwartz, Ernst; Kasprian, Gregor; Gruber, Gerlinde M.; Prayer, Daniela; Schöpf, Veronika; Langs, Georg

    2014-01-01

    The functional connectivity architecture of the adult human brain enables complex cognitive processes, and exhibits a remarkably complex structure shared across individuals. We are only beginning to understand its heterogeneous structure, ranging from a strongly hierarchical organization in sensorimotor areas to widely distributed networks in areas such as the parieto-frontal cortex. Our study relied on the functional magnetic resonance imaging (fMRI) data of 32 fetuses with no detectable morphological abnormalities. After adapting functional magnetic resonance acquisition, motion correction, and nuisance signal reduction procedures of resting-state functional data analysis to fetuses, we extracted neural activity information for major cortical and subcortical structures. Resting fMRI networks were observed for increasing regional functional connectivity from 21st to 38th gestational weeks (GWs) with a network-based statistical inference approach. The overall connectivity network, short range, and interhemispheric connections showed sigmoid expansion curve peaking at the 26–29 GW. In contrast, long-range connections exhibited linear increase with no periods of peaking development. Region-specific increase of functional signal synchrony followed a sequence of occipital (peak: 24.8 GW), temporal (peak: 26 GW), frontal (peak: 26.4 GW), and parietal expansion (peak: 27.5 GW). We successfully adapted functional neuroimaging and image post-processing approaches to correlate macroscopical scale activations in the fetal brain with gestational age. This in vivo study reflects the fact that the mid-fetal period hosts events that cause the architecture of the brain circuitry to mature, which presumably manifests in increasing strength of intra- and interhemispheric functional macro connectivity. PMID:25374531

  11. Correction of congenital diaphragmatic hernia in utero VIII: Response of the hypoplastic lung to tracheal occlusion.

    Science.gov (United States)

    Harrison, M R; Adzick, N S; Flake, A W; VanderWall, K J; Bealer, J F; Howell, L J; Farrell, J A; Filly, R A; Rosen, M A; Sola, A; Goldberg, J D

    1996-10-01

    Most fetuses with congenital diaphragmatic hernia (CDH) diagnosed before 24 weeks' gestation die despite optimal postnatal care. In fetuses with liver herniation into the chest, prenatal repair has not been successful. In the course of exploring the pathophysiology of CDH and its repair in fetal lambs, the authors found that obstructing the normal egress of fetal lung fluid enlarges developing fetal lungs, reduces the herniated viscera, and accelerates lung growth, resulting in improved pulmonary function after birth. They developed and tested experimentally a variety of methods to temporarily occlude the fetal trachea, allow fetal lung growth, and reverse the obstruction at birth. The authors applied this strategy of temporary tracheal occlusion in eight human fetuses with CDH and liver herniation at 25 to 28 weeks' gestation. With ongoing experimental and clinical experience, the technique of tracheal occlusion evolved from an internal plug (two patients) to an external clip (six patients), and a technique was developed for unplugging the trachea at the time of birth (Ex Utero Intrapartum Tracheoplasty [EXIT]). Two fetuses had a foam plug placed inside the trachea. The first showed dramatic lung growth in utero and survived; the second (who had a smaller plug to avoid tracheomalacia) showed no demonstrable lung growth and died at birth. Two fetuses had external spring-loaded aneurysm clips placed on the trachea; one was aborted due to tocolytic failure, and the other showed no lung growth (presumed leak) and died 3 months after birth. Four fetuses had metal clips placed on the trachea. All showed dramatic lung growth in utero, with reversal of pulmonary hypoplasia documented after birth. However, all died of nonpulmonary causes. Temporary occlusion of the fetal trachea accelerates fetal lung growth and ameliorates the often fatal pulmonary hypoplasia associated with severe CDH. Although the strategy is physiologically sound and technically feasible, complications

  12. From research to practice: an integrative framework for the development of interventions for children with fetal alcohol spectrum disorders.

    Science.gov (United States)

    Kodituwakku, Piyadasa W; Kodituwakku, E Louise

    2011-06-01

    Since fetal alcohol syndrome was first described over 35 years ago, considerable progress has been made in the delineation of the neurocognitive profile in children with prenatal alcohol exposure. Preclinical investigators have made impressive strides in elucidating the mechanisms of alcohol teratogenesis and in testing the effectiveness of pharmacological agents and dietary supplementation in the amelioration of alcohol-induced deficits. Despite these advances, only limited progress has been made in the development of evidence-based comprehensive interventions for functional impairment in alcohol-exposed children. Having performed a search in PubMed and PsycINFO using key words, interventions, treatment, fetal alcohol syndrome, prenatal alcohol exposure, and fetal alcohol spectrum disorders, we found only 12 papers on empirically-based interventions. Only two of these interventions had been replicated and none met the criteria of "well-established," as defined by Chambless and Hollon (Journal of Consulting and Clinical Psychology 66(1):7-18, 1998). There has been only limited cross-fertilization of ideas between preclinical and clinical research with regard to the development of interventions. Therefore, we propose a framework that allows integrating data from preclinical and clinical investigations to develop comprehensive intervention programs for children with fetal alcohol spectrum disorders. This framework underscores the importance of multi-level evaluations and interventions.

  13. Maternal obesity leads to increased proliferation and numbers of astrocytes in the developing fetal and neonatal mouse hypothalamus.

    Science.gov (United States)

    Kim, Dong Won; Glendining, Kelly A; Grattan, David R; Jasoni, Christine L

    2016-10-01

    Maternal obesity during pregnancy is associated with chronic maternal, placental, and fetal inflammation; and it elevates the risk for offspring obesity. Changes in the development of the hypothalamus, a brain region that regulates body weight and energy balance, are emerging as important determinants of offspring risk, but such changes are only beginning to be defined. Here we focused on the hypothesis that the pathological exposure of developing hypothalamic astrocytes to cytokines would alter their development. A maternal high-fat diet (mHFD) mouse model was used to investigate changes in hypothalamic astrocytes in the fetus during late gestation and in early neonates by using immunochemistry, confocal microscopy, and qPCR. The number of astrocytes and the proportion of proliferating astrocytes was significantly higher in the arcuate nucleus (ARC) and the supraoptic nucleus (SON) of the hypothalamus at both ages compared to control offspring from normal weight pregnancies. Supplemental to this we found that cultured fetal hypothalamic astrocytes proliferated significantly in response to IL6 (10ng/ml), one of the cytokines significantly elevated in fetuses of obese dams, via the JAK/STAT3 signaling pathway. Thus, maternal obesity during pregnancy stimulated the proliferation and thereby increased numbers of astrocytes in the fetal as well as early neonatal hypothalamus, which may be driven, during fetal life, by IL6. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

  14. Altered Pulmonary Lymphatic Development in Infants with Chronic Lung Disease

    Directory of Open Access Journals (Sweden)

    Emily M. McNellis

    2014-01-01

    Full Text Available Pulmonary lymphatic development in chronic lung disease (CLD has not been investigated, and anatomy of lymphatics in human infant lungs is not well defined. Hypothesis. Pulmonary lymphatic hypoplasia is present in CLD. Method. Autopsy lung tissues of eighteen subjects gestational ages 22 to 40 weeks with and without history of respiratory morbidity were stained with monoclonal antipodoplanin and reviewed under light microscopy. Percentage of parenchyma podoplanin stained at the acinar level was determined using computerized image analysis; 9 CLD and 4 control subjects gestational ages 27 to 36 weeks were suitable for the analysis. Results. Distinct, lymphatic-specific staining with respect to other vascular structures was appreciated in all gestations. Infants with and without respiratory morbidity had comparable lymphatic distribution which extended to the alveolar ductal level. Podoplanin staining per parenchyma was increased and statistically significant in the CLD group versus controls at the alveolar ductal level (0.06% ± 0.02% versus 0.04% ± 0.01%, 95% CI −0.04% to −0.002%, P<0.03. Conclusion. Contrary to our hypothesis, the findings show that there is an increase in alveolar lymphatics in CLD. It is suggested that the findings, by expanding current knowledge of CLD pathology, may offer insight into the development of more effective therapies to tackle CLD.

  15. CT Lung Cancer Screening Program Development: Part 2.

    Science.gov (United States)

    Yates, Teri

    2015-01-01

    Radiology administrators must use innovative strategies around clinical collaboration and marketing to ensure that patients access the service in sufficient numbers. Radiology Associates of South Florida in collaboration with Baptist Health South Florida have developed a successful lung cancer screening program. The biggest factors in their success have been the affordability of their service and the quality of the program. Like mammography, lung cancer screening programs serve as an entry point to other services that generate revenue for the hospital. Patients may require further evaluation in the form of more imaging or surgical services for biopsy. Part 1 provided background and laid out fundamentals for starting a program. Part 2 focuses on building patient volume, marketing, and issues related to patient management after the screen is performed.

  16. Fetal Membrane Ultrastructure and Development in the Oviparous Milksnake Lampropeltis triangulum (Colubridae) with Reference to Function and Evolution in Snakes.

    Science.gov (United States)

    Kim, Young K; Blackburn, Daniel G

    2016-07-01

    In eggs of oviparous reptiles, fetal membranes maintain developing embryos through the exchange of respiratory gases and provision of water and calcium. As part of a survey of reptilian fetal membranes, we used scanning electron microscopy to study fetal membrane morphology in the oviparous Pueblan milksnake, Lampropeltis triangulum campbelli. The chorioallantois initially is an avascular structure lined by enlarged chorionic and allantoic epithelia. Upon vascularization, the chorionic epithelium becomes greatly attenuated, enhancing the potential for gas exchange; the allantoic epithelium also flattens. The bilaminar omphalopleure of the yolk sac lacks blood vessels, but it becomes vascularized by allantoic capillaries and transformed into an omphalallantois. Upon regression of the isolated yolk mass, this membrane is converted to chorioallantois, equipping it for gas exchange. Allantoic fluid serves as a water reservoir, and we postulate that it facilitates water uptake by establishing an osmotic gradient. Early in development, epithelia of both the chorion and the omphalopleure show apical microvilli that greatly increase the cell surface area available for water uptake. However, these features are incompatible with gas exchange and are lost as oxygen needs take precedence. A comparison of the fetal membranes to those of other squamate species (both oviparous and viviparous) reveals characteristics that are probably ancestral for snakes, some of which are plesiomorphic for Squamata. The widespread phylogenetic distribution of these features reflects their utility as adaptations that serve functional requirements of squamate embryos.

  17. Development of fetal yawn compared with non-yawn mouth openings from 24-36 weeks gestation.

    Directory of Open Access Journals (Sweden)

    Nadja Reissland

    Full Text Available BACKGROUND: Although some research suggests that fetuses yawn, others disagree arguing that is it simple mouth opening. Furthermore there is no developmental account of fetal yawning compared with simple mouth opening. The aim of the present study was to establish in a repeated measures design the development of fetal yawning compared with simple mouth opening. METHODOLOGY/FINDINGS: Video recordings were made of the fetal face and upper torso visualized by means of 4D full frontal or facial profile ultrasound recordings. Fifteen healthy fetuses were scanned four times at 24, 28, 32 and 36 weeks gestation. Yawning was distinguished from non-yawning in terms of the length of time it took to reach the apex of the mouth stretch, with yawns being defined as more than 50% of the total time observed. To assess changes in frequency, a Poisson mixed effects model was fitted to the count of number of yawn and simple mouth opening events with age and gender as fixed effects, and person as a random effect. For both yawns and simple mouth openings a smooth varying age effect was significant. The number of yawns observed declined with age from 28 weeks gestation, whereas simple mouth openings were less frequent and the decline was observed from 24 weeks. Gender was not significant either for yawn and simple mouth openings. CONCLUSIONS/SIGNIFICANCE: Yawning can be reliably distinguished from other forms of mouth opening with the potential of using yawning as an index of fetal healthy development.

  18. [The influence of hyperleptinemia during pregnancy on fetal weight and obesity development in progeny mice with agouti yellow mutation].

    Science.gov (United States)

    Makarova, E N; Syracheva, M S; Bazhan, N M

    2014-03-01

    Maternal obesity increases the risk of obesity in the offspring, and obesity is accompanied by an increase in blood leptin levels. Leptin can influence the progeny metabolism via its influence on fetal growth and, possibly, via its action on AgRP expression in placenta. The "yellow" mutation at the mouse agouti locus (A(y)) evokes obesity and increases blood leptin levels in pregnant mice. The aim was to examine the influence of A(y) mutation in pregnant mice on fetal weight, placental expression of AgRP gene and food intake and obesity development in progeny. A(y) pregnant females as compared to control ones had increased circulating leptin levels on days 13 and 18 of pregnancy. Both fetal weight and placental expression of AgRP gene were increased on day 13 of pregnancy and decreased on day 18 of pregnancy in A(y) females as compared to control ones. Both control (a/a) and obesity prone (A(y)/a) male young born to A(y) mothers had lowered body weight and enhanced food intake between 5 and 11 weeks of age as compared to male progeny of control mothers. The enhanced leptin levels during pregnancy in mice are associated with retardation of obesity development in obesity prone male offspring and with changes in fetal weight and AgRP gene expression in placenta.

  19. Desenvolvimento do testículo de camundongo da fase fetal até a idade adulta Development of the mouse testis from fetal period to adulthood

    Directory of Open Access Journals (Sweden)

    Rozangela de Lucca Martins Sachetim

    1999-07-01

    Full Text Available O desenvolvimento do testículo de camundongo foi estudado desde o 15º dia de gestação até a idade adulta. As lâminas preparadas para estudo histológico em microscópio óptico foram tratadas pela técnica do ácido periódico - Schiff e pela hematoxilina de Harris (PAS + H. Na fase fetal, os túbulos seminíferos estão constituídos por gonócitos e células de sustentação imaturas. No tecido intersticial, observam-se as células de Leydig. A espermatogênese inicia-se logo após o nascimento. O epitélio seminífero torna-se mais espesso aos 14 dias pós-natal, onde se observam espermatócitos em prófase meiótica. Aos 21 dias pós-natal, o epitélio seminífero contém espermatogônias, espermatócitos e células de Sertoli. As primeiras espermátides são observadas aos 28 dias pós-natal e, aos 42 dias, já ocorrem espermátides maduras. Desde os 49 dias pós-natal, são observados espermatozóides na luz dos túbulos seminíferos. A partir dos 56 dias pós-natal, o epitélio seminífero, bem como o tecido intersticial, apresentam aspecto e características típicos do testículo do camundongo adulto.The development of mouse testis was studied from 15th day of fetal life up to adult age. The prepared slides for histological study in light microscopy were stained by periodic acid - Schiff and Haematoxylin of Harris (PAS + H. The results show that in fetal life the seminiferous tubules are constituted by gonocytes and immature sustentation cells. In the interstitial tissue, Leydig cells are found. Spermatogenesis begins soon after birth. The seminiferous epithelium becomes thicker at day 14 postnatal when spermatocytes in meiotic prophase are observed. At day 21 postnatal the seminiferous epithelium contains spermatogonia, spermatocytes and Sertoli cells. The first spermatids are observed at day 28 postnatal and at day 42 postnatal mature spermatids occur. From day 56 postnatal on the seminiferous epithelium, as well as the

  20. Impulsive aggressiveness of pregnant women affects the development of the fetal heart.

    Science.gov (United States)

    Koelsch, Stefan; Wiebigke, Claudia; Siebel, Walter A; Stepan, Holger

    2009-12-01

    Mounting evidence indicates that the development of the fetus is heavily influenced by the intra-uterine milieu during pregnancy, and that such influence may have life-long consequences for the individual. The intra-uterine milieu is not only influenced by nutritional factors, but also by maternal endocrine and autonomic activity. Such activity is prone to be affected by an individual's personality, but only little is known about influences of maternal personality on the development of the fetus. We tested pregnant women for their propensity for impulsive, uncontrollable outbursts of temper (referred to here as moderate Intermittent Explosive Disorder, mIED). After the women gave birth, we measured electrocardiograms (ECGs) from their newborn infants to compare ECGs between newborns of women with and without mIED. The data show that infants of women with mIED have larger QRS complexes in the electrocardiogram, and lower heart rate variability, compared to infants of women without mIED. These results reveal effects of maternal mIED on the fetal heart development. These effects may predispose the individual to increased risk for later cardio-vascular disease. The findings open perspectives for better risk prevention models for the unborn child.

  1. Biological monitoring of embrio-fetal exposure to methamidophos or chlorothalonil on rat development.

    Science.gov (United States)

    de Castro, V L; Chiorato, S H; Pinto, N F

    2000-12-01

    Maternal exposure to pesticides during the pre-implantation and very early post-implantation periods of pregnancy is correlated with numerous adverse effects on the offspring and in reproductive parameters like an increase in resorption, a decrease in fetal survival and weight, and teratogenic effects. Although the epidemiological evidence is inconclusive as regards the risk of the adverse outcome of pregnancy and developmental toxicity events, the use of biomarkers in exposure assessment may contribute to recognizing a potential health impairment. The present study evaluated the influence of prenatal oral exposure to an insecticide (1.0 mg methamidophos/kg) or a fungicide (200.0 mg chlorothalonil/kg) during gestation days 1 to 6 on maturational and behavioral aspects of offspring development of rats. The pesticides did not affect the body weight gain of dams and offspring, nor did the exposure affect the weight of gravid uterus, fetus, placenta and ovary. There were no observed alterations in the swimming behavior tested at postnatal days 7, 14 and 21, but the pesticides interfered with physical and maturational development landmarks of offspring according to age, showing subtle effects on behavioral and physical development. These findings show the importance of categorizing developmental effects, establishing the relationship between age and important performances, to recognize potential impacts on human populations.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-04-15

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

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

    NARCIS (Netherlands)

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

    2011-01-01

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

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

    NARCIS (Netherlands)

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

    2011-01-01

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

  5. Comparative Characterization of Cardiac Development Specific microRNAs: Fetal Regulators for Future.

    Science.gov (United States)

    Rustagi, Yashika; Jaiswal, Hitesh K; Rawal, Kamal; Kundu, Gopal C; Rani, Vibha

    2015-01-01

    MicroRNAs (miRNAs) are small, conserved RNAs known to regulate several biological processes by influencing gene expression in eukaryotes. The implication of miRNAs as another player of regulatory layers during heart development and diseases has recently been explored. However, there is no study which elucidates the profiling of miRNAs during development of heart till date. Very limited miRNAs have been reported to date in cardiac context. In addition, integration of large scale experimental data with computational and comparative approaches remains an unsolved challenge.The present study was designed to identify the microRNAs implicated in heart development using next generation sequencing, bioinformatics and experimental approaches. We sequenced six small RNA libraries prepared from different developmental stages of the heart using chicken as a model system to produce millions of short sequence reads. We detected 353 known and 703 novel miRNAs involved in heart development. Out of total 1056 microRNAs identified, 32.7% of total dataset of known microRNAs displayed differential expression whereas seven well studied microRNAs namely let-7, miR-140, miR-181, miR-30, miR-205, miR-103 and miR-22 were found to be conserved throughout the heart development. The 3'UTR sequences of genes were screened from Gallus gallus genome for potential microRNA targets. The target mRNAs were appeared to be enriched with genes related to cell cycle, apoptosis, signaling pathways, extracellular remodeling, metabolism, chromatin remodeling and transcriptional regulators. Our study presents the first comprehensive overview of microRNA profiling during heart development and prediction of possible cardiac specific targets and has a big potential in future to develop microRNA based therapeutics against cardiac pathologies where fetal gene re-expression is witnessed in adult heart.

  6. Comparative Characterization of Cardiac Development Specific microRNAs: Fetal Regulators for Future.

    Directory of Open Access Journals (Sweden)

    Yashika Rustagi

    Full Text Available MicroRNAs (miRNAs are small, conserved RNAs known to regulate several biological processes by influencing gene expression in eukaryotes. The implication of miRNAs as another player of regulatory layers during heart development and diseases has recently been explored. However, there is no study which elucidates the profiling of miRNAs during development of heart till date. Very limited miRNAs have been reported to date in cardiac context. In addition, integration of large scale experimental data with computational and comparative approaches remains an unsolved challenge.The present study was designed to identify the microRNAs implicated in heart development using next generation sequencing, bioinformatics and experimental approaches. We sequenced six small RNA libraries prepared from different developmental stages of the heart using chicken as a model system to produce millions of short sequence reads. We detected 353 known and 703 novel miRNAs involved in heart development. Out of total 1056 microRNAs identified, 32.7% of total dataset of known microRNAs displayed differential expression whereas seven well studied microRNAs namely let-7, miR-140, miR-181, miR-30, miR-205, miR-103 and miR-22 were found to be conserved throughout the heart development. The 3'UTR sequences of genes were screened from Gallus gallus genome for potential microRNA targets. The target mRNAs were appeared to be enriched with genes related to cell cycle, apoptosis, signaling pathways, extracellular remodeling, metabolism, chromatin remodeling and transcriptional regulators. Our study presents the first comprehensive overview of microRNA profiling during heart development and prediction of possible cardiac specific targets and has a big potential in future to develop microRNA based therapeutics against cardiac pathologies where fetal gene re-expression is witnessed in adult heart.

  7. Development of a fetal weight chart using serial trans-abdominal ultrasound in an East African population

    DEFF Research Database (Denmark)

    Schmiegelow, Christentze; Scheike, Thomas Harder; Oesterholt, Mayke

    2012-01-01

    trans-abdominal ultrasound. All pregnancies with pathology were excluded and a chart representing the optimal growth potential was developed using fetal weights and birth weights. The weight chart was compared to a chart from Congo, a chart representing a white population, and a chart representing......Objective: To produce a fetal weight chart representative of a Tanzanian population, and compare it to weight charts from Sub-Saharan Africa and the developed world. Methods: A longitudinal observational study in Northeastern Tanzania. Pregnant women were followed throughout pregnancy with serial......, in the end of pregnancy, the 10th percentiles deviated substantially causing an overestimation of the true prevalence of SGA newborns if our chart had not been used. Conclusions: We developed a weight chart representative for a Tanzanian population and provide evidence for the necessity of developing...

  8. Morphometric Development of Sphincter of Oddi in Human Fetuses During Fetal Period: Microscopic Study

    Directory of Open Access Journals (Sweden)

    E. Hilal Evcil

    2012-09-01

    Full Text Available Objective: In this study, morphometric developments of the sphincter of Oddi in human fetuses were observed. Material and Methods: We observed 113 human fetuses consisting of 67 male and 46 female subjects, whose ages varied between 14 to 40 weeks who showed no signs of any pathology or anomaly externally. The common external measurements of fetuses were carried out, followed by abdominal dissection to determine where the sphincters of Oddi were localized within the duodenum and pancreas. Histological specimens of tissue samples were gathered from the inner wall of the duodenum where it was assumed that the sphincters of Oddi had been localized. The parameters of total external diameters, lumen diameters, wall thickness, diameters of ductus choledochus and ductus pancreaticus, and the distance between these two structures, which are also known as the origins of the sphincter of Oddi, were measured by using a light microscope. The standard deviations of the measurements were calculated for each gestational week and trimester. Results: The calculations suggested that there were statistically significant correlations between gestational age and all of the other parameters with the exception of the ductus choledochus (p0.05.Conclusion: The data we collected in our study were considered as useful for the evaluation of the development of the sphincter of Oddi area and fetal stage.

  9. Effect of fetal undernutrition and postnatal overfeeding on rat adipose tissue and organ growth at early stages of postnatal development.

    Science.gov (United States)

    Munoz-Valverde, D; Rodríguez-Rodríguez, P; Gutierrez-Arzapalo, P Y; López de Pablo, A L; Carmen González, M; López-Giménez, R; Somoza, B; Arribas, S M

    2015-01-01

    Intrauterine and perinatal life are critical periods for programming of cardiometabolic diseases. However, their relative role remains controversial. We aimed to assess, at weaning, sex-dependent alterations induced by fetal or postnatal nutritional interventions on key organs for metabolic and cardiovascular control. Fetal undernutrition was induced by dam food restriction (50 % from mid-gestation to delivery) returning to ad libitum throughout lactation (Maternal Undernutrition, MUN, 12 pups/litter). Postnatal overfeeding (POF) was induced by litter size reduction from normally fed dams (4 pups/litter). Compared to control, female and male MUN offspring exhibited: 1) low birth weight and accelerated growth, reaching similar weight and tibial length by weaning, 2) increased glycemia, liver and white fat weights; 3) increased ventricular weight and tendency to reduced kidney weight (males only). Female and male POF offspring showed: 1) accelerated growth; 2) increased glycemia, liver and white fat weights; 3) unchanged heart and kidney weights. In conclusion, postnatal accelerated growth, with or without fetal undernutrition, induces early alterations relevant for metabolic disease programming, while fetal undernutrition is required for heart abnormalities. The progression of cardiac alterations and their role on hypertension development needs to be evaluated. The similarities between sexes in pre-pubertal rats suggest a role of sex-hormones in female protection against programming.

  10. Maternal-fetal unit interactions and eutherian neocortical development and evolution

    Directory of Open Access Journals (Sweden)

    Juan F Montiel

    2013-07-01

    Full Text Available The conserved brain design that primates inherited from early mammals differs from the variable adult brain size and species-specific brain dominances observed across mammals. This variability relies on the emergence of specialized cerebral cortical regions and sub-compartments, triggering an increase in brain size, areal interconnectivity and histological complexity that ultimately lies on the activation of developmental programs. Structural placental features are not well correlated with brain enlargement; however, several endocrine pathways could be tuned with the activation of neuronal progenitors in the proliferative neocortical compartments. In this article, we reviewed some mechanisms of eutherians maternal-fetal unit interactions associated with brain development and evolution. We propose a hypothesis of brain evolution where proliferative compartments in primates become activated by 'non-classical' endocrine placental signals participating in different steps of corticogenesis. Changes in the inner placental structure, along with placenta endocrine stimuli over the cortical proliferative activity would allow mammalian brain enlargement with a concomitant shorter gestation span, as an evolutionary strategy to escape from parent-offspring conflict.

  11. Effects of fried potato chip supplementation on mouse pregnancy and fetal development.

    Science.gov (United States)

    El-Sayyad, Hassan I; Abou-Egla, Mohamed H; El-Sayyad, Fawkia I; El-Ghawet, Heba A; Gaur, Rajiv L; Fernando, Augusta; Raj, Madhwa H G; Ouhtit, Allal

    2011-03-01

    Acrylamide (ACR), a proven rodent carcinogen, is present at significantly high quantities in commonly consumed foods such as potato chips, raising a health concern worldwide. The effects of ACR and fried potato chips (FPC) on pregnant mice and their offspring before and after birth were investigated and compared. In the pregnant mice, similar histologic abnormalities were found in various tissues for ACR intoxication and FPC supplementation. Drastic alterations were mainly seen in the liver, kidney, heart muscle, and epiphyseal cartilage of experimental dams. ACR and FPC increased the rate of abortion and neonatal mortality and decreased the total number, body weight, size, and crown-rump length of the offspring before and after birth. Interestingly, however, higher rates of congenital malformations were observed in the FPC-treated group. Although ossification of axial and appendicular bones was markedly retarded during fetal development, some ossified bones were missing in newly born offspring of treated groups. Furthermore, the incidence of missing ossification centers was higher in the FPC-treated than in the ACR-treated neonates. These results suggest that FPC can cause hazardous health effects and warrant a systematic study on the health effects of consumption of FPC and French fries in the general population. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Maternal-fetal unit interactions and eutherian neocortical development and evolution

    Science.gov (United States)

    Montiel, Juan F.; Kaune, Heidy; Maliqueo, Manuel

    2013-01-01

    The conserved brain design that primates inherited from early mammals differs from the variable adult brain size and species-specific brain dominances observed across mammals. This variability relies on the emergence of specialized cerebral cortical regions and sub-compartments, triggering an increase in brain size, areal interconnectivity and histological complexity that ultimately lies on the activation of developmental programs. Structural placental features are not well correlated with brain enlargement; however, several endocrine pathways could be tuned with the activation of neuronal progenitors in the proliferative neocortical compartments. In this article, we reviewed some mechanisms of eutherians maternal–fetal unit interactions associated with brain development and evolution. We propose a hypothesis of brain evolution where proliferative compartments in primates become activated by “non-classical” endocrine placental signals participating in different steps of corticogenesis. Changes in the inner placental structure, along with placenta endocrine stimuli over the cortical proliferative activity would allow mammalian brain enlargement with a concomitant shorter gestation span, as an evolutionary strategy to escape from parent-offspring conflict. PMID:23882189

  13. Fetal development of ligaments around the tarsal bones with special reference to contribution of muscles.

    Science.gov (United States)

    Uchiyama, Eiichi; Kim, Ji Hyun; Abe, Hiroshi; Cho, Baik Hwan; Rodríguez-Vázquez, Jose Francisco; Murakami, Gen

    2014-04-01

    Through a histological examination of eight mid-term human fetuses (10-15 weeks) and seven late-stage fetuses (30-34 weeks), we attempted to determine how and when fetal ligaments around the tarsal bones form the regular arrangement seen in adults. Ligaments along the dorsal aspect of the tarsal bones developed early as an elongation of the perichondrium, in contrast to the late development of the plantar-sided ligaments. In contrast, a distal elongation of the tibialis posterior tendon was a limited plantar ligament in the early stage; finally, it extended from the navicular, ran obliquely to cross the dorsal side of the fibularis longus tendon, and inserted to the lateral cuneiform and fourth metatarsal. In the late stage, the adductor hallucis muscle origin provided multiple ligamentous structures along the cuneiforms and metatarsals. The tarsal sinus contained multiple fibrous bundles (possibly, the putative interosseous talocalcanean ligaments) that were derived from (1) insertion tendons of the extensor digitorus brevis muscle and (2) the fibrous sheath of the extensor digitorus longus tendon. The aponeurotic origin of the quadratus plantae muscle seemed to contribute to formation of the long plantar ligament. Therefore, tarsal ligaments appeared likely to develop from the long tendons, their fibrous sheaths and aponeuroses and intramuscular tendons of the proper foot muscles. Under in utero conditions with little or no stress from the plantar side of the foot, the muscle-associated connective tissue seems to play a crucial role in providing a regular arrangement of the ligaments in accordance with tensile stress from muscle contraction. Copyright © 2013 Wiley Periodicals, Inc.

  14. CpG sites with continuously increasing or decreasing methylation from early to late human fetal brain development.

    Science.gov (United States)

    Schneider, Eberhard; Dittrich, Marcus; Böck, Julia; Nanda, Indrajit; Müller, Tobias; Seidmann, Larissa; Tralau, Tim; Galetzka, Danuta; El Hajj, Nady; Haaf, Thomas

    2016-10-30

    Normal human brain development is dependent on highly dynamic epigenetic processes for spatial and temporal gene regulation. Recent work identified wide-spread changes in DNA methylation during fetal brain development. We profiled CpG methylation in frontal cortex of 27 fetuses from gestational weeks 12-42, using Illumina 450K methylation arrays. Sites showing genome-wide significant correlation with gestational age were compared to a publicly available data set from gestational weeks 3-26. Altogether, we identified 2016 matching developmentally regulated differentially methylated positions (m-dDMPs): 1767m-dDMPs were hypermethylated and 1149 hypomethylated during fetal development. M-dDMPs are underrepresented in CpG islands and gene promoters, and enriched in gene bodies. They appear to cluster in certain chromosome regions. M-dDMPs are significantly enriched in autism-associated genes and CpGs. Our results promote the idea that reduced methylation dynamics during fetal brain development may predispose to autism. In addition, m-dDMPs are enriched in genes with human-specific brain expression patterns and/or histone modifications. Collectively, we defined a subset of dDMPs exhibiting constant methylation changes from early to late pregnancy. The same epigenetic mechanisms involving methylation changes in cis-regulatory regions may have been adopted for human brain evolution and ontogeny. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  15. [Air pollutant exposure during pregnancy and fetal and early childhood development. Research protocol of the INMA (Childhood and Environment Project)].

    Science.gov (United States)

    Esplugues, Ana; Fernández-Patier, Rosalía; Aguilera, Inma; Iñíguez, Carmen; García Dos Santos, Saúl; Aguirre Alfaro, Amelia; Lacasaña, Marina; Estarlich, Marisa; Grimalt, Joan O; Fernández, Marieta; Rebagliato, Marisa; Sala, María; Tardón, Adonina; Torrent, Maties; Martínez, María Dolores; Ribas-Fitó, Núria; Sunyer, Jordi; Ballester, Ferran

    2007-01-01

    The INMA (INfancia y Medio Ambiente [Spanish for Environment and Childhood]) project is a cooperative research network. This project aims to study the effects of environment and diet on fetal and early childhood development. This article aims to present the air pollutant exposure protocol during pregnancy and fetal and early childhood development of the INMA project. The information to assess air pollutant exposure during pregnancy is based on outdoor measurement of air pollutants (nitrogen dioxide [NO2], volatile organic compounds [VOC], ozone, particulate matter [PM10, PM2,5 ] and of their composition [polycyclic aromatic hydrocarbons]); measurement of indoor and personal exposure (VOC and NO2); urinary measurement of a biological marker of hydrocarbon exposure (1-hydroxypyrene); and data gathered by questionnaires and geographic information systems. These data allow individual air pollutant exposure indexes to be developed, which can then be used to analyze the possible effects of exposure on fetal development and child health. This protocol and the type of study allow an approximation to individual air pollutant exposure to be obtained. Finally, the large number of participants (N = 4,000), as well as their geographic and social diversity, increases the study's potential.

  16. Fetal congenital lobar emphysema.

    Science.gov (United States)

    Chia, Chun-Chieh; Huang, Soon-Cen; Liu, Min-Chang; Se, Tung-Yi

    2007-03-01

    To report a rare fetal congenital lung anomaly characterized by over inflation of a pulmonary lobe. A 28-year-old systemic lupus erythematous mother, gravida 1 para 0, who had normal prenatal care in our department, was admitted for labor pain and an abnormal fetal heart location was noted incidentally during labor. The baby showed rib retraction in room air but no obvious cyanotic change after delivery. Both the fetus chest X-ray and ultrasound showed a hyperechogenic tumor in the left thoracic cavity with a right-side-shifted heart and trachea. Computed tomography showed a hypodense and multiseptal tumor in the left thoracic cavity with right-sided shift of the heart and trachea. It was a soft, solid tumor in the parenchyma of the left lung and the histopathology confirmed it to be benign congenital lobar emphysema. The favorable outcome in both asymptomatic and mildly symptomatic children suggests that a nonsurgical approach should be considered for these patients.

  17. Quantitative CT characterization of pediatric lung development using routine clinical imaging

    Energy Technology Data Exchange (ETDEWEB)

    Stein, Jill M.; Brody, Alan S.; Fleck, Robert J. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Walkup, Laura L. [Cincinnati Children' s Hospital Medical Center, Center for Pulmonary Imaging Research, Pulmonary Medicine and Radiology, Cincinnati, OH (United States); Woods, Jason C. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Cincinnati Children' s Hospital Medical Center, Center for Pulmonary Imaging Research, Pulmonary Medicine and Radiology, Cincinnati, OH (United States)

    2016-12-15

    The use of quantitative CT analysis in children is limited by lack of normal values of lung parenchymal attenuation. These characteristics are important because normal lung development yields significant parenchymal attenuation changes as children age. To perform quantitative characterization of normal pediatric lung parenchymal X-ray CT attenuation under routine clinical conditions in order to establish a baseline comparison to that seen in pathological lung conditions. We conducted a retrospective query of normal CT chest examinations in children ages 0-7 years from 2004 to 2014 using standard clinical protocol. During these examinations semi-automated lung parenchymal segmentation was performed to measure lung volume and mean lung attenuation. We analyzed 42 CT examinations in 39 children, ages 3 days to 83 months (mean ± standard deviation [SD] = 42 ± 27 months). Lung volume ranged 0.10-1.72 liters (L). Mean lung attenuation was much higher in children younger than 12 months, with values as high as -380 Hounsfield units (HU) in neonates (lung volume 0.10 L). Lung volume decreased to approximately -650 HU by age 2 years (lung volume 0.47 L), with subsequently slower exponential decrease toward a relatively constant value of -860 HU as age and lung volume increased. Normal lung parenchymal X-ray CT attenuation decreases with increasing lung volume and age; lung attenuation decreases rapidly in the first 2 years of age and more slowly thereafter. This change in normal lung attenuation should be taken into account as quantitative CT methods are translated to pediatric pulmonary imaging. (orig.)

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

    OpenAIRE

    Erickson, Anders C; Laura Arbour

    2014-01-01

    Exposure to particulate air pollution and socioeconomic risk factors are shown to be independently associated with adverse pregnancy outcomes; however, their confounding relationship is an epidemiological challenge that requires understanding of their shared etiologic pathways affecting fetal-placental development. The purpose of this paper is to explore the etiological mechanisms associated with exposure to particulate air pollution in contributing to adverse pregnancy outcomes and how these...

  19. Asymmetry of Radial and Symmetry of Tangential Neuronal Migration Pathways in Developing Human Fetal Brains.

    Science.gov (United States)

    Miyazaki, Yuta; Song, Jae W; Takahashi, Emi

    2016-01-01

    The radial and tangential neural migration pathways are two major neuronal migration streams in humans that are critical during corticogenesis. Corticogenesis is a complex process of neuronal proliferation that is followed by neuronal migration and the formation of axonal connections. Existing histological assessments of these two neuronal migration pathways have limitations inherent to microscopic studies and are confined to small anatomic regions of interest (ROIs). Thus, little evidence is available about their three-dimensional (3-D) fiber pathways and development throughout the entire brain. In this study, we imaged and analyzed radial and tangential migration pathways in the whole human brain using high-angular resolution diffusion MR imaging (HARDI) tractography. We imaged ten fixed, postmortem fetal (17 gestational weeks (GW), 18 GW, 19 GW, three 20 GW, three 21 GW and 22 GW) and eight in vivo newborn (two 30 GW, 34 GW, 35 GW and four 40 GW) brains with no neurological/pathological conditions. We statistically compared the volume of the left and right radial and tangential migration pathways, and the volume of the radial migration pathways of the anterior and posterior regions of the brain. In specimens 22 GW or younger, the volume of radial migration pathways of the left hemisphere was significantly larger than that of the right hemisphere. The volume of posterior radial migration pathways was also larger when compared to the anterior pathways in specimens 22 GW or younger. In contrast, no significant differences were observed in the radial migration pathways of brains older than 22 GW. Moreover, our study did not identify any significant differences in volumetric laterality in the tangential migration pathways. These results suggest that these two neuronal migration pathways develop and regress differently, and radial neuronal migration varies regionally based on hemispheric and anterior-posterior laterality, potentially explaining regional differences in

  20. Vascular endothelial growth factor co-ordinates proper development of lung epithelium and vasculature.

    Science.gov (United States)

    Zhao, Liqing; Wang, Ke; Ferrara, Napoleone; Vu, Thiennu H

    2005-07-01

    The vasculature forms an intrinsic functional component of the lung and its development must be tightly regulated and coordinated with lung epithelial morphogenesis. Vascular endothelial growth factor (VEGF) and its receptors are highly expressed in a complementary pattern in the lungs during embryonic development. VEGF is expressed by epithelium and the receptors in the surrounding mesenchyme. To determine the function of VEGF in lung formation, we inhibited its activity using a soluble receptor in lung renal capsule grafts. Inhibition of VEGF results in inhibition of vascular development and significant alteration in epithelial development. Epithelial proliferation is inhibited, sacculation is impaired, and the epithelium undergoes apoptosis. Interestingly, when VEGF is attenuated, epithelial differentiation still proceeds, as shown by acquisition of both proximal and distal markers. These data show that VEGF co-ordinates epithelial and vascular development. It is required for the development of the lung vasculature and the vasculature is necessary for epithelial proliferation and morphogenesis, but not for cell differentiation.

  1. Effect of the exogenons glucocorticoid on GR expression in fetal rat lung%外源性糖皮质激素对胎鼠肺糖皮质激素受体基因的作用

    Institute of Scientific and Technical Information of China (English)

    宋丽

    2001-01-01

    Objective To investigate the effect of glucocorticoid receptor(GR)in late gestation fetal lung around the time of the onset of augmented surfactant production. Methods GR mRNA was meaanred by Northern blots and hybridizations. GR binding activity was measured by Wrang's method. Results Maternal administration of a high dose dexamethatone increased fetal rat lung GR binding activity, without alteration in GR mRNA levels. Also incubation of fibroblasts (FIB)with 10-7 mol/L cortisol increased GR immunoreactive protein and binding activity without affecting GR mRNA. Identical treatment, epithelial eells(EPI)were followed by decrease of GR protein without changes of GR mRNA. Conclusion The regulation of GR by glucocorticoid in fetal rat lung occurs at a posttranscriptional level, and increasing circulation glucocorticoid concentration during late gestation may be important to the maturation of fetal lung.%目的研究糖皮质激素在妊娠后期肺表面活性物质合成过程中对糖皮质激素受体(GR)的调节作用。方法采用分子生物学杂交技术、Northern印迹法测定胎鼠肺及其二种主要细胞的GR mRNA及Wrang法测定外源性糖皮质激素对胎鼠肺及二种主要细胞GR结合活性的作用。结果大剂量地塞米松可使胎鼠肺GR结合活性增加而GR mRNA无变化。在成纤维细胞(FIB)培养液中加入10-7mol/L的可的松,GR结合活性和蛋白量增加,GRmRNA无变化。上皮细胞(EPI)GR蛋白量减少,GR mRNA无变化,肺表面活性物质蛋白(SP-A)经同样处理其值增加。结论胎鼠肺GR的调节发生于转译后水平,妊娠后期使用糖皮质激素对胎鼠的成熟有重要生理意义。

  2. Antenatal Steroid Therapy for Fetal Lung Maturation and the Subsequent Risk of Childhood Asthma: A Longitudinal Analysis

    Directory of Open Access Journals (Sweden)

    Jason D. Pole

    2010-01-01

    adjusted hazard ratio for 5–7 years was 1.06 (95% confidence interval: 0.86, 1.30 and for 8 or greater years was 0.74 (95% confidence interval: 0.54, 1.03. Antenatal steroid therapy appears to be an independent risk factor for the development of asthma between 3 and 5 years of age.

  3. Bi-iliac distance and iliac bone position compared to the vertebral column in normal fetal development

    DEFF Research Database (Denmark)

    Hartling, U B; Fischer Hansen, B; Skovgaard, L T

    2001-01-01

    Prenatal standards of bi-iliac width were not found in the literature based on autopsy investigations, nor was the caudo-cranial position of the ilia compared to the vertebral column. The first purpose of the present study was to establish normal standard values for the bi-iliac distance in fetal...... life, the second to evaluate the level of the iliac bones proportional to the ossified vertebral column. Whole body radiographs in antero-posterior projections from 98 human fetuses (36 female and 44 male fetuses, as well as 18 fetuses on which the sex had not been determined) were analyzed...... caliper. The caudo-cranial position of the iliac bones was evaluated. The present study shows that in normal fetal development there is a continuous linear enlargement of the pelvic region in the transverse and vertical planes. The upper iliac contour stays at the level of the first sacral vertebral body...

  4. The 2008 National Institute of Child Health and Human Development workshop report on electronic fetal monitoring: update on definitions, interpretation, and research guidelines

    National Research Council Canada - National Science Library

    Macones, George A; Hankins, Gary D V; Spong, Catherine Y; Hauth, John; Moore, Thomas

    2008-01-01

    In April 2008, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine...

  5. Effect of exogenous insulin administration on ovarian function, embryo/fetal development during pregnancy in goats.

    Science.gov (United States)

    Suguna, K; Mehrotra, S; Agarwal, S K; Hoque, M; Shanker, U; Singh, S K; Varshney, V P

    2009-04-01

    The effect of insulin was investigated on ovarian follicle population, ovulation rate, hormonal profiles and embryo/fetal development during pregnancy using transrectal ultrasonography in goats. Twelve goats synchronized in estrus were selected for the experiment. They were divided into two groups, viz. (untreated control, n=6) and (insulin treated, n=6). In treated group long acting bovine insulin was administered @ 0.2IU/kg body weight subcutaneously for three consecutive days, i.e. days 7-9 of estrous cycle. Thereafter, weekly single injection of insulin was continued for rest of the experiment. However, in control group only normal saline was injected as placebo. Breeding was allowed by natural service in both the groups. The does were subjected to B-mode transrectal ultrasound scanning of ovary and uterus weekly up to 120 and 98 days of gestation, respectively. Blood samples were collected weekly up to 135 days of gestation for the estimation of estradiol 17beta and progesterone (P4). The result revealed no difference in mean number of total follicles between the control and insulin treated groups. The diameter of medium follicle did not differ where as diameter of large follicle was comparatively higher in treated than control goats. The average number of corpus luteum (CL) was higher in insulin treated group as compared to control (1.66 vs. 1.16). However, the number as well as mean diameter of CL did not differ significantly between treated and control group. Serum concentrations of estradiol 17beta and progesterone were significantly (P0.05) in treated animals. The results demonstrated beneficial effect of exogenous administration of insulin on ovarian function and twinning percentage in goats.

  6. Fetal development of the elastic-fiber-mediated enthesis in the human middle ear.

    Science.gov (United States)

    Takanashi, Yoshitaka; Shibata, Shunichi; Katori, Yukio; Murakami, Gen; Abe, Shinichi; Rodríguez-Vázquez, Jose Francisco; Kawase, Tetsuaki

    2013-10-01

    In the human middle ear, the annular ligament of the incudostapedial joint and the insertions of the tensor tympani and stapedius muscles contain abundant elastic fibers; i.e., the elastic-fiber-mediated entheses. Hyaluronan also coexists with the elastic fibers. In the present study using immunohistochemistry, we demonstrated the distribution of elastin not only in the incudostapedial joint but also in the other two joints of the middle ear in adults and fetuses. In adults, the expression of elastin did not extend out of the annular ligament composed of mature elastic fibers but clearly overlapped with it. Electron microscopic observations of the annular ligament demonstrated a few microfibrils along the elastic fibers. Thus, in contrast to the vocal cord, the middle ear entheses seemed not to contain elaunin and oxytalan fibers. In mid-term fetuses (at approximately 15-16 weeks of gestation) before opening of the external acoustic meatus, the incudostapedial joint showed abundant elastic fibers, but the incudomalleolar and stapediovestibular joints did not. At this stage, hyaluronan was not colocalized, but distributed diffusely in loose mesenchymal tissues surrounding the ear ossicles. Therefore, fetal development of elastin and elastic fibers in the middle ear entheses is unlikely to require acoustic oscillation. In late-stage fetuses (25-30 weeks), whose ear ossicles were almost the same size as those in adults, we observed bundling and branching of elastic fibers. However, hyaluronan expression was not as strong as in adults. Colocalization between elastic fibers and hyaluronan appeared to be a result of postnatal maturation of the entheses.

  7. Development and morphogenesis of human wrist joint during embryonic and early fetal period.

    Science.gov (United States)

    Hita-Contreras, Fidel; Martínez-Amat, Antonio; Ortiz, Raúl; Caba, Octavio; Alvarez, Pablo; Prados, José C; Lomas-Vega, Rafael; Aránega, Antonia; Sánchez-Montesinos, Indalecio; Mérida-Velasco, Juan A

    2012-06-01

    The development of the human wrist joint has been studied widely, with the main focus on carpal chondrogenesis, ligaments and triangular fibrocartilage. However, there are some discrepancies concerning the origin and morphogenetic time-table of these structures, including nerves, muscles and vascular elements. For this study we used serial sections of 57 human embryonic (n = 30) and fetal (n = 27) specimens from O'Rahilly stages 17-23 and 9-14 weeks, respectively. The following phases in carpal morphogenesis have been established: undifferentiated mesenchyme (stage 17), condensated mesenchyme (stages 18 and 19), pre-chondrogenic (stages 19 and 20) and chondrogenic (stages 21 and over). Carpal chondrification and osteogenic processes are similar, starting with capitate and hamate (stage 19) and ending with pisiform (stage 22). In week 14, a vascular bud penetrates into the lunate cartilaginous mold, early sign of the osteogenic process that will be completed after birth. In stage 18, median, ulnar and radial nerves and thenar eminence appear in the hand plate. In stage 21, there are indications of the interosseous muscles, and in stage 22 flexor digitorum superficialis, flexor digitorum profundus and lumbrical muscles, transverse carpal ligament and collateral ligaments emerge. In stage 23, the articular disc, radiocarpal and ulnocarpal ligaments and deep palmar arterial arch become visible. Radiate carpal and interosseous ligaments appear in week 9, and in week 10, dorsal radiocarpal ligament and articular capsule are evident. Finally, synovial membrane is observed in week 13. We have performed a complete analysis of the morphogenesis of the structures of the human wrist joint. Our results present new data on nervous and arterial elements and provide the basis for further investigations on anatomical pathology, comparative morphology and evolutionary anthropology. © 2012 The Authors. Journal of Anatomy © 2012 Anatomical Society.

  8. Sex Moderates Associations between Prenatal Glucocorticoid Exposure and Human Fetal Neurological Development

    Science.gov (United States)

    Glynn, Laura M.; Sandman, Curt A.

    2012-01-01

    Maternal cortisol levels (at 15, 19, 25, 31 and 37 weeks' gestation) and fetal movement response to vibroacoustic stimulation (VAS; at 25, 31 and 37 weeks) were assessed in 190 mother-fetus pairs. Fetuses showed a response to the VAS at 25 weeks and there was evidence of increasing maturation in the response at 31 and 37 weeks. Early elevations in…

  9. Development and trafficking function of haematopoietic stem cells and myeloid cells during fetal ontogeny

    NARCIS (Netherlands)

    Heinig, Kristina; Sage, Fanny; Robin, Catherine; Sperandio, Markus

    2015-01-01

    Fetal haematopoiesis is a highly regulated process in terms of time and location. It is characterized by the emergence of specific cell populations at different extra-and intraembryonic anatomical sites. Trafficking of haematopoietic stem cells (HSCs) between these supportive niches is regulated by

  10. Development and trafficking function of haematopoietic stem cells and myeloid cells during fetal ontogeny

    NARCIS (Netherlands)

    Heinig, Kristina; Sage, Fanny; Robin, Catherine; Sperandio, Markus

    2015-01-01

    Fetal haematopoiesis is a highly regulated process in terms of time and location. It is characterized by the emergence of specific cell populations at different extra- and intraembryonic anatomical sites. Trafficking of haematopoietic stem cells (HSCs) between these supportive niches is regulated by

  11. Vigilancia Fetal

    OpenAIRE

    SAONA UGARTE, Pedro

    2013-01-01

    La percepción de la actividad fetal por la madre es la técnica más antigua y menos costosa de controlar el bienestar fetal. Tradicionalmente se ha considerado la disminución o ausencia de movimientos fetales percibidos por la madre, como una señal de alarma, en especial cuando existe insuficiencia útero placentaria. Varios investigadores han descrito el valor del registro diario de movimientos fetales como un método para identificar el feto en peligrote morir. El poder discernir si el feto se...

  12. Maternal synchronization of gestational length and lung maturation.

    Directory of Open Access Journals (Sweden)

    Valérie Besnard

    Full Text Available Among all mammals, fetal growth and organ maturation must be precisely synchronized with gestational length to optimize survival at birth. Lack of pulmonary maturation is the major cause of infant mortality in preterm birth. Whether fetal or maternal genotypes influence the close relationship between the length of gestation and lung function at birth is unknown. Structural and biochemical indicators of pulmonary maturity were measured in two mouse strains whose gestational length differed by one day. Shorter gestation in C57BL/6J mice was associated with advanced morphological and biochemical pulmonary development and better perinatal survival when compared to A/J pups born prematurely. After ovarian transplantation, A/J pups were born early in C57BL/6J dams and survived after birth, consistent with maternal control gestational length. Expression of genes critical for perinatal lung function was assessed in A/J pups born after ovarian transfer. A subset of mRNAs important for perinatal respiratory adaptation was selectively induced in the A/J pups born after ovarian transfer. mRNAs precociously induced after ovarian transfer indicated an important role for the transcription factors C/EBPα and CREB in maternally induced lung maturation. We conclude that fetal lung maturation is determined by both fetal and maternal genotypes. Ovarian transfer experiments demonstrated that maternal genotype determines the timing of birth and can influence fetal lung growth and maturation to ensure perinatal survival.

  13. Immunotherapy and lung cancer: current developments and novel targeted therapies.

    Science.gov (United States)

    Domingues, Duarte; Turner, Alice; Silva, Maria Dília; Marques, Dânia Sofia; Mellidez, Juan Carlos; Wannesson, Luciano; Mountzios, Giannis; de Mello, Ramon Andrade

    2014-01-01

    Non-small-cell lung cancer (NSCLC) is a highly prevalent and aggressive disease. In the metastatic setting, major advances include the incorporation of immunotherapy and targeted therapies into the clinician's therapeutic armamentarium. Standard chemotherapeutic regimens have long been reported to interfere with the immune response to the tumor; conversely, antitumor immunity may add to the effects of those therapies. The aim of immunotherapy is to specifically enhance the immune response directed to the tumor. Recently, many trials addressed the role of such therapies for metastatic NSCLC treatment: ipilimumab, tremelimumab, nivolumab and lambrolizumab are immunotherapeutic agents of main interest in this field. In addition, anti-tumor vaccines, such as MAGE-A3, Tecetomide, TG4010, CIMAvax, ganglioside vaccines, tumor cell vaccines and dendritic cell vaccines, emerged as potent inducers of immune response against the tumor. The current work aims to address the most recent developments regarding these innovative immunotherapies and their implementation in the treatment of metastatic NSCLC.

  14. Sex and gender differences in lung development and their clinical significance

    NARCIS (Netherlands)

    Boezen, HA; Jansen, DF; Postma, DS

    2004-01-01

    Because little is known about the development of lung parenchyma, this article focuses on developmental airway changes. The lung continues to develop throughout most of a person's life. Alterations to bronchi and bronchioli during the distinct phases of early life (ie, human intrauterine development

  15. Endotoxin induced chorioamnionitis prevents intestinal development during gestation in fetal sheep.

    Directory of Open Access Journals (Sweden)

    Tim G A M Wolfs

    junctional protein ZO-1, the immune defence and vascular function are immature at low GA and are further compromised by endotoxin-induced chorioamnionitis. This study suggests that both prematurity and inflammation in utero disturb fetal gut development, potentially predisposing to postnatal intestinal pathology.

  16. An immunocytochemical study of the germinal layer vasculature in the developing fetal brain using Ulex europaeus 1 lectin.

    Science.gov (United States)

    Gould, S J; Howard, S

    1988-10-01

    The characteristics of the germinal matrix vasculature were studied in the developing fetal brain using immunocytochemical methods. A preliminary comparative immunocytochemical study was made on six fetal brains to compare endothelial staining by Ulex europaeus I lectin with that of antibody to Factor VIII related antigen. Ulex was found to stain germinal layer vessels better than Factor VIII related antigen. Subsequently, the germinal layers of a further 15 fetal and preterm infant brains ranging from 13 to 35 weeks' gestation were stained with Ulex europaeus I to demonstrate the vasculature. With increasing gestation, there was a gradual increase in vessel density, particularly of capillaries. This was not a uniform process. A plexus of capillaries was prominent immediately beneath the ependyma while the more central parts of the germinal matrix contained fewer, but often larger diameter, vessels. The variation in vessel density which was a feature of the later gestation brains may have implications for local blood flow and may be a factor in haemorrhage at this site.

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

    Directory of Open Access Journals (Sweden)

    Keith M Godfrey

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

  18. Clearance of refractory ceramic fibers (RCF) from the rat lung: development of a model.

    Science.gov (United States)

    Yu, C P; Zhang, L; Oberdörster, G; Mast, R W; Glass, L R; Utell, M J

    1994-05-01

    Chronic exposure and postexposure experiments have been recently performed in rats to evaluate the biological responses of inhaled refractory ceramic fibers (RCF) at different concentration levels. The lung burden data in the accessory lobe of the rat lung were collected during and after different exposure and postexposure periods. The size distribution of retained fibers in the lung at different time points was also measured. We used these data to develop a mathematical model of fiber clearance from the rat lung. It was found that the clearance rate did not depend significantly upon fiber size but there was a clear dependence on lung burden. As lung burden increased, the clearance rate was found to decrease. An empirical equation was derived for the clearance rate as a function of lung burden. At low burdens, rats had a retention half-time of about 126 days for RCF compared to a typical half-time of about 60 days for insoluble nonfibrous particles.

  19. Fetal pain.

    Science.gov (United States)

    Rokyta, Richard

    2008-12-01

    The fetus reacts to nociceptive stimulations through different motor, autonomic, vegetative, hormonal, and metabolic changes relatively early in the gestation period. With respect to the fact that the modulatory system does not yet exist, the first reactions are purely reflexive and without connection to the type of stimulus. While the fetal nervous system is able to react through protective reflexes to potentially harmful stimuli, there is no accurate evidence concerning pain sensations in this early period. Cortical processes occur only after thalamocortical connections and pathways have been completed at the 26th gestational week. Harmful (painful) stimuli, especially in fetuses have an adverse effect on the development of humans regardless of the processes in brain. Moreover, pain activates a number of subcortical mechanisms and a wide spectrum of stress responses influence the maturation of thalamocortical pathways and other cortical activation which are very important in pain processing.

  20. Development of LC-QTOF-MS method for human lung tissue fingerprinting. A preliminary application to nonsmall cell lung cancer.

    Science.gov (United States)

    Ciborowski, Michal; Kisluk, Joanna; Pietrowska, Karolina; Samczuk, Paulina; Parfieniuk, Ewa; Kowalczyk, Tomasz; Kozlowski, Miroslaw; Kretowski, Adam; Niklinski, Jacek

    2017-09-01

    The major histologic subtypes of non-small cell lung cancer (NSCLC) include adenocarcinoma (ADC), squamous cell lung carcinoma (SCC), and large-cell carcinoma (LCC). Clinical trials of targeted agents and newer chemotherapy agents yielded differences in outcomes according to histologic subgroups providing a rationale for histology-based treatment in NSCLC. Currently, NSCLC subtyping is performed based on histopathological examinations and immunohistochemistry. However available methods leave about 10% of NSCLC cases as not otherwise specified. The purpose of this study was development of an LC-QTOF-MS method for human lung tissue metabolic fingerprinting that could discriminate NSCLC histological subtypes and propose biomarkers candidates that could support proper NSCLC diagnosis. Metabolites were extracted with acetonitrile or methanol/ethanol and different chromatographic conditions were tested. In the final method 10 mg of lung tissue was homogenized with 50% methanol and metabolites were extracted with acetonitrile. Metabolites were separated on C8-RP and HILIC columns. About 3500 and 2000 of metabolic features (in both ion modes) were detected with good repeatability (CV Lung tumor and control tissue samples obtained from NSCLC patients were analyzed with developed methodology. Acylcarnitines, fatty acids, phospholipids, and amino acids were found more abundant in tumor as compared to control tissue. Acylcarnitines, lysophospholipids, creatinine, creatine, and alanine were identified as potential targets enabling classification of NSCLC subtypes. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. The Impact of Umbilical Blood Flow Regulation on Fetal Development Differs in Diabetic and Non-Diabetic Pregnancy

    Directory of Open Access Journals (Sweden)

    Jian Li

    2014-09-01

    Full Text Available Background/Aims: Diabetes is well-known to influence endothelial function. Endothelial function and blood flow regulation might be different in diabetic and non-diabetic pregnancy. However, the impact of umbilical blood flow regulation in gestational diabetes on fetal development is unknown so far. Methods: In a prospective birth cohort study, we analyzed the association of the umbilical artery Doppler indices (pulsatility index, resistance index and systolic/diastolic ratio and fetal size measures (biparietal diameter, head circumference, abdominal circumference, femur length and birth weight in 519 non-gestational diabetes mellitus pregnancies (controls and 226 gestational diabetes mellitus pregnancies in middle (day 160.32 ±16.29 of gestation and late (day 268.12 ±13.04 of gestation pregnancy. Results: Multiple regression analysis considering confounding factors (gestational day of ultrasound examination, offspring sex, maternal body mess index before pregnancy, maternal age at delivery, maternal body weight at delivery and maternal hypertension showed that umbilical artery Doppler indices (pulsatility index, resistance index and systolic/diastolic ratio were associated with fetal head circumference and femur length in middle gestational diabetes mellitus pregnancy but not in non-gestational diabetes mellitus pregnancy. Head circumference, biparietal diameter, abdominal circumference and femur length in mid gestation were smaller in fetus of gestational diabetes mellitus pregnancy versus non-gestational diabetes mellitus pregnancy. In contrast to non-gestational diabetes mellitus pregnancy in late gestation, umbilical artery Doppler indices in gestational diabetes mellitus pregnancy were not associated with ultrasound measures of fetal growth. Birth weight was slightly increased in gestational diabetes mellitus pregnancy as compared to non-gestational diabetes mellitus pregnancy. Conclusions: The impact of umbilical blood flow on fetal

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

    Science.gov (United States)

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

    2012-08-01

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

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

    Science.gov (United States)

    Hau, J; Basse, A; Wolstrup, C

    1987-01-01

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

  4. The Monocarboxylate Transporter Inhibitor α-Cyano-4-Hydroxycinnamic Acid Disrupts Rat Lung Branching

    Directory of Open Access Journals (Sweden)

    Sara Granja

    2013-12-01

    Full Text Available Background/Aims: The human embryo develops in a hypoxic environment. In this way, cells have to rely on the glycolytic pathway for energy supply, leading to an intracellular accumulation of monocarboxylates such as lactate and pyruvate. These acids have an important role in cell metabolism and their rapid transport across the plasma membrane is crucial for the maintenance of intracellular pH homeostasis. This transport is mediated by a family of transporters, designated by monocarboxylate transporters (MCTs, namely isoforms 1 and 4. MCT1/4 expression is regulated by the ancillary protein CD147.The general aim of this study was to characterize the expression pattern of MCT1/4, CD147 and the glucose transporter GLUT1 during human fetal lung development and elucidate the role of MCTs in lung development. Methods: The expression pattern of MCT1/4 and GLUT1 was characterized by immunohistochemistry and fetal lung viability and branching were evaluated by exposing rat fetal lung explants to CHC, an inhibitor of MCT activity. Results: Our findings show that all the biomarkers are differently expressed during fetal lung development and that CHC appears to have an inhibitory effect on lung branching and viability, in a dose dependent way. Conclusion: We provide evidence for the role of MCTs in embryo lung development, however to prove the dependence of MCT activity further studies are waranted.

  5. Fetal pain?

    Science.gov (United States)

    Vanhatalo, S; van Nieuwenhuizen, O

    2000-05-01

    During the last few years a vivid debate, both scientifically and emotionally, has risen in the medical literature as to whether a fetus is able to feel pain during abortion or intrauterine surgery. This debate has mainly been inspired by the demonstration of various hormonal or motor reactions to noxious stimuli at very early stages of fetal development. The aims of this paper are to review the literature on development of the pain system in the fetus, and to speculate about the relationship between "sensing" as opposed to "feeling" pain and the number of reactions associated with painful stimuli. While a cortical processing of pain theoretically becomes possible after development of the thalamo-cortical connections in the 26th week of gestation, noxious stimuli may trigger complex reflex reactions much earlier. However, more important than possible painfulness is the fact that the noxious stimuli, by triggering stress responses, most likely affect the development of an individual at very early stages. Hence, it is not reasonable to speculate on the possible emotional experiences of pain in fetuses or premature babies. A clinically relevant aim is rather to avoid and/or treat any possibly noxious stimuli, and thereby prevent their potential adverse effects on the subsequent development.

  6. Effect of Preeclampsia on Fetal Lung Maturity and Its Action Mechanism%子痫前期对胎鼠肺成熟的影响及其机制研究

    Institute of Scientific and Technical Information of China (English)

    祝秀; 曾万江; 乔福元; 刘海意; 吴媛媛; 张莹

    2013-01-01

    目的 探讨子痫前期对胎鼠肺成熟的影响及其机制.方法 将孕鼠分为子痫前期早产组(preeclampsia preterm group,PPG)、非子痫前期足月产对照组(non-preeclampsia fullterm group,NPFG)与非子痫前期早产对照组(non-preeclampsia preterm group,NPPG),使用N-硝基-L-精氨酸甲酯(L-NAME)建立子痫前期动物模型,无菌操作取出胎鼠肺,每组随机取胎肺用于组织切片,进行苏木精-伊红染色,镜下观察胎鼠肺气管及肺泡的发育情况;应用实时荧光定量PCR技术(Real-time PCR)及Western blot技术检测缺氧诱导因子-1α(HIF-1α)、血管内皮生长因子(VEGF)、表面活性蛋白B(SP-B)及表面活性蛋白C(SP-C)mRNA及蛋白水平的表达情况.结果 组织切片染色显示子痫前期早产组胎肺血管及气管发育相对于非子痫前期早产对照组更好;组织Real-time PCR及Western blot检测结果 显示:非子痫前期足月产对照组HIF-1α、VEGF、SP-B与SP-C mRNA及蛋白表达水平明显高于非子痫前期早产对照组及子痫前期早产组,差异有统计学意义(均P<0.05);子痫前期早产组HIF-1α与VEGF mRNA及蛋白表达水平比非子痫前期早产对照组升高,差异有统计学意义(均P<0.05);子痫前期早产组SP-C 与SP-B mRNA及蛋白表达水平与非子痫前期早产对照组差异无统计学意义(均P>0.05).结论 子痫前期能促进胎肺的结构成熟,但对肺泡功能无明显影响.%Objective To examine the effect of preeclampsia on fetal lung maturity. Methods The Wistar pregnant rats were randomly divided into control group and model group in which the rats were intraperitoneally injected with L-NAME. The pathological changes of the fetal rat lung were observed by HE staining. The mRNA and protein expression levels of HIF-1 alpha , VEGF, SP-B and SP-C were detected by using real-time PCR and Western blot. Results HE staining showed that the development of pulmonary vessels and the trachea in preeclampsia

  7. 产前超声诊断胎儿肺部异常及预后评估%Prenatal Diagnosis of Fetal Congenital Disease of Lung and Clinical Prognosis by Ultrasound

    Institute of Scientific and Technical Information of China (English)

    陆冰; 姜小力; 殷林亮; 邓学东

    2015-01-01

    Objective To describe the antenatalfi ndings and outcome of fetuses with congenital lung disease. MethodsA total of 147 cases of fetal congenital disease of lung were diagnosed and the data was retrospectively analyzed.Results 1. Among the 147 fetuses of congenital lung disease, there were 89 lung lesion; 59 cases of pleural effusion (PE), 4 case of echogenic lung; 1 case of pulmonary hypopasia with ribs malformation and 1 case of pulmonary agenesis (PA); 2. 49 patients with other pulmonary abnormalities, including: fetal edema, lymph hydroma, congenital heart malformation, skeletal deformities, hepatic cyst, heart shift, Bilateral hydronephrosis, single umbilical artery and amnioticfl uid; 3. Fetal outcome: a total of 97 cases of fetus performed induced abortion, 10 cases of disease spontaneous regression before labor, 40 cases of lesions persist and choose to continue pregnancy.ConclusionPrenatal ultrasonography has a high accuracy rate for the diagnosis and classification of fetal congenital lung disease. For different types of pulmonary lesions need to be carefully identifi ed. With detailed observation of the fetus and prenatal follow-up, ultrasonography is helpful to predict the clinical outcome of the fetus.%目的:探讨胎儿肺部异常的产前超声特征及评估临床预后价值。方法对147例产前超声诊断有胎儿肺部异常的胎儿声像图进行回顾性分析。结果①147例肺部异常的胎儿中产前检出89例团块样病变;检出胸腔积液共59例,检出4例肺回声弥漫性增强;1例肺发育不良伴有肋骨畸形;1例肺缺如。②49例伴发其他肺部异常,包括:胎儿水肿、淋巴水囊瘤、心脏畸形、骨骼畸形、肝囊肿、心脏移位、双肾积水、单脐动脉、羊水过多;③胎儿临床结局:147例共有97例胎儿选择引产,10例病变产前自行消退,40例病灶持续存在并选择继续妊娠。结论对于肺部病灶的不同类型诊断需要谨慎鉴别,

  8. Fetal-to-maternal signaling to initiate parturition.

    Science.gov (United States)

    Reinl, Erin L; England, Sarah K

    2015-07-01

    Multiple processes are capable of activating the onset of parturition; however, the specific contributions of the mother and the fetus to this process are not fully understood. In this issue of the JCI, Gao and colleagues present evidence that steroid receptor coactivators 1 and 2 (SRC-1 and SRC-2) regulate surfactant protein-A (SP-A) and platelet-activating factor (PAF) expression, which increases in the developing fetal lung. WT dams crossed with males deficient for both SRC-1 and SRC-2 had suppressed myometrial inflammation, increased serum progesterone, and delayed parturition, which could be reconciled by injection of either SP-A or PAF into the amnion. Together, the results of this study demonstrate that the fetal lungs produce signals to initiate labor in the mouse. This work underscores the importance of the fetus as a contributor to the onset of murine, and potentially human, parturition.

  9. Fetal-to-maternal signaling to initiate parturition

    Science.gov (United States)

    Reinl, Erin L.; England, Sarah K.

    2015-01-01

    Multiple processes are capable of activating the onset of parturition; however, the specific contributions of the mother and the fetus to this process are not fully understood. In this issue of the JCI, Gao and colleagues present evidence that steroid receptor coactivators 1 and 2 (SRC-1 and SRC-2) regulate surfactant protein-A (SP-A) and platelet-activating factor (PAF) expression, which increases in the developing fetal lung. WT dams crossed with males deficient for both SRC-1 and SRC-2 had suppressed myometrial inflammation, increased serum progesterone, and delayed parturition, which could be reconciled by injection of either SP-A or PAF into the amnion. Together, the results of this study demonstrate that the fetal lungs produce signals to initiate labor in the mouse. This work underscores the importance of the fetus as a contributor to the onset of murine, and potentially human, parturition. PMID:26098207

  10. In utero exposure to environmentally relevant concentrations of PCB 153 and PCB 118 disrupts fetal testis development in sheep.

    Science.gov (United States)

    Krogenæs, Anette K; Ropstad, Erik; Gutleb, Arno C; Hårdnes, Nina; Berg, Vidar; Dahl, Ellen; Fowler, Paul A

    2014-01-01

    Polychlorinated biphenyls (PCB) are environmental pollutants linked to adverse health effects including endocrine disruption and disturbance of reproductive development. This study aimed to determine whether exposure of pregnant sheep to three different mixtures of PCB 153 and PCB 118 affected fetal testis development. Ewes were treated by oral gavage from mating until euthanasia (d 134), producing three groups of fetuses with distinct adipose tissue PCB levels: high PCB 153/low PCB 118 (n = 13), high PCB 118/low PCB 153 (n = 14), and low PCB 153/low PCB 118 (n = 14). Fetal testes and blood samples were collected for investigation of testosterone, testis morphology, and testis proteome. The body weight of the offspring was lower in the high PCB compared to the low PCB group, but there were no significant differences in testis weight between groups when corrected for body weight. PCB exposure did not markedly affect circulating testosterone. There were no significant differences between groups in number of seminiferous tubules, Sertoli cell only tubules, and ratio between relative areas of seminiferous tubules and interstitium. Two-dimensional (2D) gel-based proteomics was used to screen for proteomic alterations in the high exposed groups relative to low PCB 153/low PCB 118 group. Twenty-six significantly altered spots were identified by liquid chromatography (LC)-mass spectroscopy (MS)/MS. Changes in protein regulation affected cellular processes as stress response, protein synthesis, and cytoskeleton regulation. The study demonstrates that in utero exposure to different environmental relevant PCB mixtures exerted subtle effects on developing fetal testis proteome but did not significantly disturb testis morphology and testosterone production.

  11. [Maternal nutrition during pregnancy conditions the fetal pancreas development, hormonal status and diabetes mellitus and metabolic syndrome biomarkers at birth].

    Science.gov (United States)

    Sánchez-Muniz, F J; Gesteiro, E; Espárrago Rodilla, M; Rodríguez Bernal, B; Bastida, S

    2013-01-01

    Pregnancy is a vital period where several hyperplasic, hypertrophic processes together with metabolic adaptation and preparation for extra-uterine life take place. Present review accounts for central aspects of nutrition throughout gestation on the embryonic and fetal periods. It is centered in the major changes occurring in fetal pancreas, with special mention to the susceptibility of this main glucose homeostasis organ to support nutritional changes during maturation and development. Studies performed in animal models as human are commented considering the role of maternal nutrition on β-cell mass size, insulin and other pancreatic hormones production, and insulin sensitivity. Details of both the thrifty genotype and phenotype hypothesis are given, indicating that hypo/subnutrition causes metabolic adaptations that permit the future body to grow and develop itself in limited environmental and energetic conditions. The Barker hypothesis is considered suggesting that this metabolic hypothesis is a double-edged sword in the actual abundance World. Lastly the review, taking into account our own research and other papers, analyses less known aspects that relate maternal diet with insulin resistance/sensitivity markers at delivery. Particularly the role of the saturated fatty acid/carbohydrate and omega-6/omega-3 ratios in the frame of maternal diet is reviewed considering the quality of those diets under the Healthy Eating Index and the Adherence to Mediterranean Diet scores and the relationship with insulin resistance profile at birth. Present review ends indicating that nutritional habits should be strongly stated before gestation in order to assure a proper nutrition since the first moment of pregnancy. This will support an adequate fetal and pancreatic growth and development, and in turn, adequate glucose homeostasis during pregnancy and later in life, slowing down or preventing from degenerative diseases related with metabolic syndrome and type 2 diabetes

  12. Expression of Nerve Growth Factor (NGF), TrkA, and p75NTR in Developing Human Fetal Teeth

    Science.gov (United States)

    Mitsiadis, Thimios A.; Pagella, Pierfrancesco

    2016-01-01

    Nerve growth factor (NGF) is important for the development and the differentiation of neuronal and non-neuronal cells. NGF binds to specific low- and high-affinity cell surface receptors, respectively, p75NTR and TrkA. In the present study, we examined by immunohistochemistry the expression patterns of the NGF, p75NTR, and TrkA proteins during human fetal tooth development, in order to better understand the mode of NGF signaling action in dental tissues. The results obtained show that these molecules are expressed in a wide range of dental cells of both epithelial and mesenchymal origin during early stages of odontogenesis, as well as in nerve fibers that surround the developing tooth germs. At more advanced developmental stages, NGF and TrkA are localized in differentiated cells with secretory capacities such as preameloblasts/ameloblasts secreting enamel matrix and odontoblasts secreting dentine matrix. In contrast, p75NTR expression is absent from these secretory cells and restricted in proliferating cells of the dental epithelium. The temporospatial distribution of NGF and p75NTR in fetal human teeth is similar, but not identical, with that observed previously in the developing rodent teeth, thus indicating that the genetic information is well-conserved during evolution. The expression patterns of NGF, p75NTR, and TrkA during odontogenesis suggest regulatory roles for NGF signaling in proliferation and differentiation of epithelial and mesenchymal cells, as well as in attraction and sprouting of nerve fibers within dental tissues. PMID:27536251

  13. Morphofunctional changes and mechanisms of their realization in developing lungs under influence of paracetamol and nimesulid

    Directory of Open Access Journals (Sweden)

    Kharchenko S.V.

    2012-01-01

    Full Text Available Actuality of organs and tissues normality development studying is conditioned on continuous growth of conge-nital abnormalies оn the base of greater drugs distribution. The anomalie s of lungs development unde r influence of paraceta-mol and nimesulide are examined and the possible mechanisms of their appearance are analysed. It is determined that lungs develop more slowly under action of paracetamol than in norm and paracetamol lead to development of bronchial asthma during postnatal period of life. Small in numbers researches of nimesulide influen ce demonstrate changes of lungs histogene-sis, which show up in thei r development deceleration.

  14. Grafts of fetal locus coeruleus neurons in rat amygdala-piriform cortex suppress seizure development in hippocampal kindling.

    Science.gov (United States)

    Barry, D I; Wanscher, B; Kragh, J; Bolwig, T G; Kokaia, M; Brundin, P; Björklund, A; Lindvall, O

    1989-11-01

    Hippocampal kindling was investigated in rats with a 6-hydroxydopamine-induced lesion of the forebrain catecholamine system after implantation of neural tissue from the fetal locus coeruleus region either bilaterally into the amygdala-piriform cortex (i.e., distant to the kindling site) or unilaterally into the hippocampus (close to the kindling site). Lesioned animals with either sham grafts or control grafts consisting of fetal striatal tissue showed a kindling rate much faster than that of normal controls. In contrast, in rats with bilateral locus coeruleus grafts in the amygdala-piriform cortex (implanted at three sites) the development of seizures was similar to that of controls and significantly slower than that in lesioned animals with sham grafts. All these animals had bilateral surviving grafts with a mean of 125 noradrenergic cells per implantation site. In the animals with locus coeruleus grafts in the stimulated hippocampus the kindling rate did not differ from that in the lesioned animals with control grafts. Most of these animals had large surviving grafts and showed a dense noradrenergic reinnervation of the implanted hippocampus. The present findings indicate that grafting of fetal pontine tissue (rich in noradrenergic neurons) to a site distant to the stimulation focus, but important for the generalization and spread of seizures, can retard the development of seizures in hippocampal kindling. Together with the data of our previous report this study also indicates that noradrenergic reinnervation of both hippocampi is important for the seizure-suppressant action in hippocampal kindling of locus coeruleus grafts implanted in the hippocampus.

  15. Smoking history and lung carcinoma: KRAS mutation is an early hit in lung adenocarcinoma development.

    NARCIS (Netherlands)

    Thunnissen, F.B.J.M.; Prinsen, C.; Hol, B.; Drift, M.A. van der; Vesin, A.; Brambilla, C.; Montuenga, L.; Field, J.K.

    2012-01-01

    BACKGROUND: In a European multicenter prospective study patients with lung cancer were interviewed for smoking history and biological samples centrally collected. The aim of this study was to compare KRAS mutation analysis with smoking status at the time of diagnosis. METHODS: A nested case-study wa

  16. Development of a metastatic fluorescent Lewis Lung carcinoma mouse model

    DEFF Research Database (Denmark)

    Rask, Lene; Fregil, Marianne; Høgdall, Estrid;

    2013-01-01

    models. To examine the mechanisms involved in tumor metastasis, we first generated a stably transfected Lewis Lung carcinoma cell line expressing a far-red fluorescent protein, called Katushka. After in vivo growth in syngeneic mice, two fluorescent Lewis Lung cancer subpopulations were isolated from...... primary tumors and lung metastases. The metastasis-derived cells exhibited a significant improvement in in vitro invasive activity compared to the primary tumor-derived cells, using a quantitative invasion chamber assay. Moreover, expression levels of 84 tumor metastasis-related mRNAs, 88 cancer......-related microRNAs as well as Dicer and Drosha were determined using RT-qPCR. Compared to the primary Lewis Lung carcinoma subculture, the metastasis-derived cells exhibited statistically significantly increased mRNA levels for several matrix metalloproteinases as well as hepatocyte growth factor (HGF...

  17. FA1 immunoreactivity in endocrine tumours and during development of the human fetal pancreas; negative correlation with glucagon expression

    DEFF Research Database (Denmark)

    Tornehave, D; Jensen, Charlotte Harken; Teisner, B;

    1996-01-01

    proteins delta and notch and to the murine preadipocyte differentiation factor Pref-1. These proteins participate in determining cell fate choices during differentiation. We now report that FA1 immunoreactivity is present in a number of neuroectodermally derived tumours as well as in pancreatic endocrine...... tumours. A negative correlation between FA1 and glucagon immunoreactants in these tumours prompted a reexamination of FA1 immunoreactants during fetal pancreatic development. At the earliest stages of development, FA1 was expressed by most of the non-endocrine parenchymal cells and, with ensuing...... development, gradually disappeared from these cells and became restricted to insulin-producing beta cells. Throughout development FA1 was not detected in endocrine glucagon, somatostatin or pancreatic polypeptide cells. Moreover, developing insulin cells that coexpressed glucagon were negative for FA1. Thus...

  18. Renal Angiomyolipoma in Pregnancy: Surgical Management with Fetal Preservation - Approach in a Developing Setting

    Science.gov (United States)

    Ugwumba, Fred O.; Nnakenyi, Emeka F.; Okafor, Okechukwu C.; Onuh, Augustine C.; Ezechukwu, Paschalina C.; Urube, Sunday

    2016-01-01

    Renal angiomyolipomas (RAML) are uncommon benign renal tumours that are associated with a tendency to rupture resulting in sometimes-torrential retroperitoneal hemorrhage as the Wunderlich syndrome or as severe potentially exsanguinating hematuria. When hemorrhage from RAML occurs in pregnancy it presents a unique challenge requiring timely and appropriately adapted intervention with the goal of preventing fatality, preserving renal function as well as preventing fetal loss if possible. We report the management of severe bleeding from RAML in pregnancy and highlight the need to adopt a management strategy that suits the practice environment and offers the patient standard and enduring care. PMID:28176962

  19. Renal angiomyolipoma in pregnancy: surgical management with fetal preservation - Approach in a developing setting

    Directory of Open Access Journals (Sweden)

    Fred O. Ugwumba

    2016-12-01

    Full Text Available Renal angiomyolipomas (RAML are uncommon benign renal tumours that are associated with a tendency to rupture resulting in sometimes- torrential retroperitoneal hemorrhage as the Wunderlich syndrome or as severe potentially exsanguinating hematuria. When hemorrhage from RAML occurs in pregnancy it presents a unique challenge requiring timely and appropriately adapted intervention with the goal of preventing fatality, preserving renal function as well as preventing fetal loss if possible. We report the management of severe bleeding from RAML in pregnancy and highlight the need to adopt a management strategy that suits the practice environment and offers the patient standard and enduring care.

  20. MR evaluation of fetal demise

    Energy Technology Data Exchange (ETDEWEB)

    Victoria, Teresa; Chauvin, Nancy Anne; Johnson, Ann M.; Kramer, Sandra Sue; Epelman, Monica [The Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); Capilla, Elena [Hospital Universitario Clinico San Carlos de Madrid, Madrid (Spain)

    2011-07-15

    Fetal demise is an uncommon event encountered at MR imaging. When it occurs, recognition by the interpreting radiologist is important to initiate appropriate patient management. To identify MR findings of fetal demise. Following IRB approval, a retrospective search of the radiology fetal MR database was conducted searching the words ''fetal demise'' and ''fetal death.'' Fetuses with obvious maceration or no sonographic confirmation of death were excluded. Eleven cases formed the study group. These were matched randomly to live fetuses of similar gestational age. Images were reviewed independently by three pediatric radiologists. The deceased fetus demonstrates decreased MR soft-tissue contrast and definition of tissue planes, including loss of gray-white matter differentiation in the brain. The signal within the cardiac chambers, when visible, is bright on HASTE sequences from the stagnant blood; the heart is small. Pleural effusions and decreased lung volumes may be seen. Interestingly, the fetal orbits lose their anatomical round shape and become smaller and more elliptical; a dark, irregular rim resembling a mask may be seen. Although fetal demise is uncommonly encountered at MR imaging, radiologists should be aware of such imaging findings so prompt management can be instituted. (orig.)

  1. Fetal Macrosomia

    Science.gov (United States)

    ... might need special care in the hospital's neonatal intensive care unit. Keep in mind that your baby might ... References Copel JA, et al. Fetal macrosomia. In: Obstetric Imaging. Philadelphia, Pa.: Saunders Elsevier; 2012. http://www. ...

  2. Fetal Ultrasound

    Science.gov (United States)

    ... needle placement during certain prenatal tests, such as amniocentesis or chorionic villus sampling. Determine fetal position before ... home. Accessed Aug. 11, 2015. Ghidini A. Diagnostic amniocentesis. http://www.uptodate.com/home. Accessed Aug. 11, ...

  3. Iroquois genes influence proximo-distal morphogenesis during rat lung development

    NARCIS (Netherlands)

    W.G. van Tuyl (Minke); J. Liu (Jason); F. Groenman (Frederick); R. Ridsdale (Ross); R.N.N. Han (Robin N.); V. Venkatesh (Vikram); D. Tibboel (Dick); M.R. Post (Martin)

    2006-01-01

    textabstractLung development is a highly regulated process directed by mesenchymal-epithelial interactions, which coordinate the temporal and spatial expression of multiple regulatory factors required for proper lung formation. The Iroquois homeobox (Irx) genes have been implicated in the patterning

  4. Fetal exposure to maternal inflammation does not affect postnatal development of genetically-driven ileitis and colitis.

    Directory of Open Access Journals (Sweden)

    Jana Hemmerling

    Full Text Available BACKGROUND: Chronic inflammatory disorders have been increasing in incidence over the past decades following geographical patterns of industrialization. Fetal exposure to maternal inflammation may alter organ functions and the offspring's disease risk. We studied the development of genetically-driven ileitis and colitis in response to maternal inflammation using mouse models. METHODS: Disease susceptible (TnfΔARE/+ and IL10-/- and disease-free (Tnf+/+ and IL10-/+ offspring were raised in inflamed and non-inflamed dams. Ileal, caecal and colonic pathology was evaluated in the offspring at 8 or 12 weeks of age. Ly6G-positive cells in inflamed sections from the distal ileum and distal colon were analysed by immunofluorescence microscopy. Gene expression of pro-inflammatory cytokines was measured in whole tissue specimens by quantitative PCR. Microarray analyses were performed on laser microdissected intestinal epithelium. Caecal bacterial communities were assessed by Illumina sequencing of 16S rRNA amplicons. RESULTS: Disease severity, the number of infiltrated neutrophils as well as Tnf and Il12p40 mRNA expression were independent of maternal inflammation in the offspring of mouse models for ileitis (TnfΔARE/+ and colitis (IL10-/-. Although TNF-driven maternal inflammation regulated 2,174 (wild type and 3,345 (TnfΔARE/+ genes in the fetal epithelium, prenatal gene expression patterns were completely overwritten after birth. In addition, co-housing experiments revealed no change in phylogenetic diversity of the offspring's caecal microbiota in response to maternal inflammation. This is independent of the offspring's genotype before and after the onset of tissue pathology. CONCLUSIONS: Disease risk and activity in mouse models of chronic ileitis and colitis was independent of the fetal exposure to maternal inflammation. Likewise, maternal inflammation did not alter the diversity and composition of offspring's caecal microbiota, clearly

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

    Science.gov (United States)

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

    1986-11-01

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

  6. Fetal pain

    OpenAIRE

    Adama van Scheltema, Phebe

    2011-01-01

    Recent studies have suggested that the fetus is capable of exhibiting a stress response to intrauterine needling, resulting in alterations in fetal stress hormone levels. Intrauterine transfusions are performed by inserting a needle either in the umbilical cord root at the placental surface (PCI), or in the intrahepatic portion of the umbilical vein (IHV). Aim of our study was to test the hypothesis that fetal hormonal changes during intrauterine transfusion are more pronounced when the needl...

  7. The MicroRNA 29 Family Promotes Type II Cell Differentiation in Developing Lung.

    Science.gov (United States)

    Guo, Wei; Benlhabib, Houda; Mendelson, Carole R

    2016-08-15

    Lung alveolar type II cells uniquely synthesize surfactant, a developmentally regulated lipoprotein that is essential for breathing. Expression of the gene (SFTPA) encoding the major surfactant protein, SP-A, in midgestation human fetal lung (HFL) is dramatically induced by cyclic AMP (cAMP). cAMP induction of SP-A expression is repressed by transforming growth factor β (TGF-β) and by hypoxia. In this study, we found that expression of the microRNA 29 (miR-29) family was significantly upregulated in epithelial cells isolated from mouse fetal lung during late gestation and in epithelial cells isolated from HFL explants during type II cell differentiation in culture. miR-29 expression in cultured HFL epithelial cells was increased by cAMP and inhibited by hypoxia, whereas the miR-29 target, TGF-β2, was coordinately decreased. Knockdown of the miR-29 family in cultured HFL type II cells blocked cAMP-induced SP-A expression and accumulation of surfactant-containing lamellar bodies, suggesting their physiological relevance. This occurred through derepression of TGF-β signaling. Notably, cAMP increased binding of endogenous thyroid transcription factor 1 (TTF-1/Nkx2.1) to the miR-29ab1 promoter in HFL type II cells, and TTF-1 increased miR-29ab1 promoter-driven luciferase activity in cotransfection assays. Together, these findings identify miR-29 family members as TTF-1-driven mediators of SP-A expression and type II cell differentiation through repression of TGF-β signaling.

  8. Effects of transcutaneous electrical nerve stimulation on fetal and placental development in an experimental model of placental insufficiency.

    Science.gov (United States)

    Guimarães, Camila S O; Gomes, Bruno B F; Oliveira, Rafael A; Yamamoto, Leandro R; Rocha, Laura P; Glória, Maria A; Machado, Juliana R; Câmara, Niels O S; Reis, Marlene A; Corrêa, Rosana R M

    2016-01-01

    To elucidate the effects of transcutaneous electrical nerve stimulation (TENS) in pregnancies with placental insufficiency. Pregnant rats were subjected to uterine artery ligation and to TENS according to the following groups: ligated stimulated (LS); ligated non-stimulated (LN), control stimulated (CS); and control non-stimulated (CN). Fetal external measurements, such as crown-rump length (CRL), fronto-occipital distance (FOD), thoracic ventral-dorsal (TVDD) and abdominal ventral-dorsal (AVDD) distances were analyzed together with the area occupied by fetal internal organs. Glucose transporter 1 (GLUT-1) expression was evaluated by immunohistochemistry in fetal organs. Thickness of junctional, labyrinth and intermediate placental zones was analyzed by morphometric evaluation in HE-stained slides, and placental hypoxia-inducible factor 1 alfa expression was measured by real-time polymerase chain reaction. In LN and CS groups compared to the CN group, CRL was reduced (27.51/28.95 versus 30.16 mm), as well as FOD (6.63/6.63 versus 7.36 mm), AVDD (7.38/8.00 versus 8.61 mm) and TVDD (6.46/6.87 versus 7.23 mm). Brain GLUT-1 expression was higher in LS (1.3%) and CS (1.8%). The area occupied by placental vessels in the labyrinth zone (29.67 ± 3.51 versus 20.83 ± 7.63) and intermediate zone (26.46 ± 10.21 versus 10.86 ± 8.94) was larger in the LS group than in the LN group. Our results suggest a negative effect of TENS on placental development, thus compromising the maintenance of adequate blood flow to the fetus.

  9. Growth in Inuit children exposed to polychlorinated biphenyls and lead during fetal development and childhood.

    Science.gov (United States)

    Dallaire, Renée; Dewailly, Éric; Ayotte, Pierre; Forget-Dubois, Nadine; Jacobson, Sandra W; Jacobson, Joseph L; Muckle, Gina

    2014-10-01

    Because of their geographical location and traditional lifestyle, Canadian Inuit children are highly exposed to polychlorinated biphenyls (PCBs) and lead (Pb), environmental contaminants that are thought to affect fetal and child growth. We examined the associations of these exposures with the fetal and postnatal growth of Inuit children. We conducted a prospective cohort study among Inuit from Nunavik (Arctic Québec). Mothers were recruited at their first prenatal visit; children (n=290) were evaluated at birth and at 8-14 years of age. Concentrations of PCB 153 and Pb were determined in umbilical cord and child blood. Weight, height and head circumference were measured at birth and during childhood. Cord blood PCB 153 concentrations were not associated with anthropometric measurements at birth or school age, but child blood PCB 153 concentrations were associated with reduced weight, height and head circumference during childhood. There was no association between cord Pb levels and anthropometric outcomes at birth, but cord blood Pb was related to smaller height and shows a tendency of a smaller head circumference during childhood. Our results suggest that chronic exposure to PCBs during childhood is negatively associated with skeletal growth and weight, while prenatal Pb exposure is related to reduced growth during childhood. This study is the first to link prenatal Pb exposure to poorer growth in school-age children. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Development of the blood-brain barrier within the paraventricular nucleus of the hypothalamus: influence of fetal glucocorticoid excess.

    Science.gov (United States)

    Frahm, Krystle A; Tobet, Stuart A

    2015-07-01

    The blood-brain barrier (BBB) is a critical contributor to brain function. To understand its development and potential function in different brain regions, the postnatal (P) BBB was investigated in the mouse cortex (CTX), lateral hypothalamus, and paraventricular nucleus of the hypothalamus (PVN). Brains were examined on postnatal days (P)12, P22 and P52 for BBB competency and for pericytes as key cellular components of the BBB demarcated by immunoreactive desmin. Glucocorticoid influences (excess dexamethasone; dex) during prenatal development were also assessed for their impact on the blood vessels within these regions postnatally. At P12, there was significantly more extravascular leakage of a low molecular weight dye (fluorescein isothiocyanate) in the CTX than within hypothalamic regions. For pericytes, there were low levels of desmin immunoreactivity at P12 that increased with age for all regions. There was more desmin immunoreactivity present in the PVN at each age examined. Fetal dex exposure resulted in decreased blood vessel density within the PVN at P20. In the CTX, dex exposure increased BBB competency, in contrast to the PVN where there was a decrease in BBB competency and increased pericyte presence. Overall, unique alterations in the functioning of the BBB within the PVN may provide a novel mechanism for fetal antecedent programming that may influence adult disorders.

  11. Effect of nebivolol treatment during pregnancy on the genital circulation, fetal growth and postnatal development in the Wistar rat.

    Science.gov (United States)

    Altoama, Kassem; Yassine Mallem, Mohamed; Thorin, Chantal; Betti, Eric; Desfontis, Jean-Claude

    2015-07-05

    The aim of study was to evaluate the effects of nebivolol, a cardioselective beta-1 adrenergic receptor blocker of the third generation with vasodilatory properties, vs. bisoprolol on the genital circulation, uterine vasculature, fetal growth and postnatal development in pregnant Wistar rats. Non invasive measurements of systolic and diastolic blood pressure (SBP and DBP) and heart rate (HR), and invasive measurement of genital blood flow (GBF) were taken in pregnant rats, by tail cuff and transonic probe methods respectively, after an oral treatment by gastric gavage with nebivolol (8mg/kg/day) or bisoprolol (10mg/kg/day) from day 11 to day 18 of pregnancy. Other morphometrical and histological measurements were performed on the ovarian and uterine arteries to evaluate the effect of nebivolol on the uterine vasculature. Furthermore, postnatal mortality and pup growth were recorded. The data demonstrated that nebivolol (compared with bisoprolol) induced a significant decrease in SBP, HR and GBF while DBP remained unchanged. Moreover, nebivolol increased the diameter and the length of ovarian and uterine arteries and the number of uterine artery segmental branches. The results also showed that the body weight gain of newborns in the nebivolol group was significantly lower vs. bisoprolol and vs. control with a higher mortality rate. The nebivolol action is not only limited to its favorable hemodynamic effects represented by a decrease in blood pressure, but it also produces adverse effects on fetal growth and postnatal development that may limit its therapeutic use in females during pregnancy.

  12. Expression of energy balance regulatory genes in the developing ovine fetal hypothalamus at midgestation and the influence of hyperglycemia.

    Science.gov (United States)

    Adam, Clare L; Findlay, Patricia A; Chanet, Audrey; Aitken, Raymond P; Milne, John S; Wallace, Jacqueline M

    2008-06-01

    Evidence suggests that the prenatal nutritional environment influences the risk of developing obesity, a major health problem worldwide. It is hypothesized that fetal nutrition influences the developing neuroendocrine hypothalamus, the integrative control center for postnatal energy balance regulation. The present aim was to determine whether relevant hypothalamic genes are expressed in midgestation and whether they are nutritionally (glucose) sensitive at this time. Hypothalami from a cohort of 81-day singleton sheep fetuses, with varying glycemia by virtue of maternal dietary and/or growth hormone treatment, were subject to in situ hybridization analysis for primary orexigenic, anorexigenic, and related receptor genes (term = 147 days, n = 24). Neuropeptide Y, agouti-related peptide, proopiomelanocortin (POMC), cocaine- and amphetamine-regulated transcript (CART), and insulin receptor mRNAs were all localized in the hypothalamic arcuate nucleus (ARC) of all fetuses, whereas leptin receptor mRNA was expressed more abundantly in the ventromedial hypothalamic nucleus. ARC expression levels of POMC and CART genes, but none of the other genes, were positively correlated with fetal plasma glucose concentrations. Therefore, key central components of adult energy balance regulation were already present as early as midgestation (equivalent to 22 wk in humans), and two anorexigenic components were upregulated by elevated glycemia. Such changes provide a potential mechanism for the prenatal origins of postnatal energy balance dysregulation and obesity.

  13. Occupational exposure to radon for underground tourist routes in Poland: Doses to lung and the risk of developing lung cancer

    Directory of Open Access Journals (Sweden)

    Katarzyna Walczak

    2017-10-01

    Full Text Available Objectives: Radon concentrations for 31 Polish underground tourist routes were analyzed. The equivalent dose to the lung, the effective dose and the relative risk were calculated for employees of the analyzed routes on the grounds of information on radon concentrations, work time, etc. Material and Methods: The relative risk for lung cancers was calculated using the Biological Effects of Ionizing Radiation (BEIR VI Committee model. Equivalent doses to the lungs of workers were determined using the coefficients calculated by the Kendall and Smith. The conversion coefficient proposed by the International Atomic Energy Agency (IAEA in the report No. 33 was used for estimating the effective doses. Results: In 13 routes, the effective dose was found to be above 1 mSv/year, and in 3 routes, it exceeded 6 mSv/year. For 5 routes, the equivalent dose to lungs was higher than 100 mSv/year, and in 1 case it was as high as 490 mSv/year. In 22.6% of underground workplaces the risk of developing lung cancer among employees was about 2 times higher than that for the general population, and for 1 tourist route it was about 5 times higher. The geometric mean of the relative risk of lung cancer for all workers of underground tourist routes was 1.73 (95% confidence interval (CI: 1.6–1.87. Routes were divided into: caves, mines, post-military underground constructions and urban underground constructions. Conclusions: The difference between levels of the relative risk of developing lung cancer for all types of underground tourist routes was not found to be significant. If we include the professional group of the employees of underground tourist routes into the group of occupational exposure, the number of persons who are included in the Category A due to occupational exposure may increase by about 3/4. The professional group of the employees of underground tourist routes should be monitored for their exposure to radon. Int J Occup Med Environ Health 2017;30(5:687

  14. Occupational exposure to radon for underground tourist routes in Poland: Doses to lung and the risk of developing lung cancer.

    Science.gov (United States)

    Walczak, Katarzyna; Olszewski, Jerzy; Politański, Piotr; Zmyślony, Marek

    2017-07-14

    Radon concentrations for 31 Polish underground tourist routes were analyzed. The equivalent dose to the lung, the effective dose and the relative risk were calculated for employees of the analyzed routes on the grounds of information on radon concentrations, work time, etc. The relative risk for lung cancers was calculated using the Biological Effects of Ionizing Radiation (BEIR) VI Committee model. Equivalent doses to the lungs of workers were determined using the coefficients calculated by the Kendall and Smith. The conversion coefficient proposed by the International Atomic Energy Agency (IAEA) in the report No. 33 was used for estimating the effective doses. In 13 routes, the effective dose was found to be above 1 mSv/year, and in 3 routes, it exceeded 6 mSv/year. For 5 routes, the equivalent dose to lungs was higher than 100 mSv/year, and in 1 case it was as high as 490 mSv/year. In 22.6% of underground workplaces the risk of developing lung cancer among employees was about 2 times higher than that for the general population, and for 1 tourist route it was about 5 times higher. The geometric mean of the relative risk of lung cancer for all workers of underground tourist routes was 1.73 (95% confidence interval (CI): 1.6-1.87). Routes were divided into: caves, mines, post-military underground constructions and urban underground constructions. The difference between levels of the relative risk of developing lung cancer for all types of underground tourist routes was not found to be significant. If we include the professional group of the employees of underground tourist routes into the group of occupational exposure, the number of persons who are included in the Category A due to occupational exposure may increase by about 3/4. The professional group of the employees of underground tourist routes should be monitored for their exposure to radon. Int J Occup Med Environ Health 2017;30(5):687-694.

  15. FGF signaling pathway in the developing chick lung: expression and inhibition studies.

    Directory of Open Access Journals (Sweden)

    Rute S Moura

    Full Text Available BACKGROUND: Fibroblast growth factors (FGF are essential key players during embryonic development. Through their specific cognate receptors (FGFR they activate intracellular cascades, finely regulated by modulators such as Sprouty. Several FGF ligands (FGF1, 2, 7, 9, 10 and 18 signaling through the four known FGFRs, have been implicated in lung morphogenesis. Although much is known about mammalian lung, so far, the avian model has not been explored for lung studies. METHODOLOGY/PRINCIPAL FINDINGS: In this study we provide the first description of fgf10, fgfr1-4 and spry2 expression patterns in early stages of chick lung development by in situ hybridization and observe that they are expressed similarly to their mammalian counterparts. Furthermore, aiming to determine a role for FGF signaling in chick lung development, in vitro FGFR inhibition studies were performed. Lung explants treated with an FGF receptor antagonist (SU5402 presented an impairment of secondary branch formation after 48 h of culture; moreover, abnormal lung growth with a cystic appearance of secondary bronchi and reduction of the mesenchymal tissue was observed. Branching and morphometric analysis of lung explants confirmed that FGFR inhibition impaired branching morphogenesis and induced a significant reduction of the mesenchyme. CONCLUSIONS/SIGNIFICANCE: This work demonstrates that FGFRs are essential for the epithelial-mesenchymal interactions that determine epithelial branching and mesenchymal growth and validate the avian embryo as a good model for pulmonary studies, namely to explore the FGF pathway as a therapeutic target.

  16. Maternal obesity induced by a high fat diet causes altered cellular development in fetal brains suggestive of a predisposition of offspring to neurological disorders in later life.

    Science.gov (United States)

    Stachowiak, Ewa K; Srinivasan, Malathi; Stachowiak, Michal K; Patel, Mulchand S

    2013-12-01

    Fetal development in an obese maternal intrauterine environment has been shown to predispose the offspring for a number of metabolic disorders in later life. The observation that a large percentage of women of child-bearing age in the US are overweight/obese during pregnancy is therefore a source of concern. A high fat (HF) diet-induced obesity in female rats has been used as a model for maternal obesity. The objective of this study was to determine cellular development in brains of term fetuses of obese rats fed a HF diet from the time of weaning. Fetal brains were dissected out on gestational day 21 and processed for immunohistochemical analysis in the hypothalamic as well as extra-hypothalamic regions. The major observation of this study is that fetal development in the obese HF female rat induced several alterations in the HF fetal brain. Marked increases were observed in orexigenic signaling and a significant decrease was observed for anorexigenic signaling in the vicinity of the 3rd ventricle in HF brains. Additionally, our results indicated diminished migration and maturation of stem-like cells in the 3rd ventricular region as well as in the brain cortex. The results from the present study indicate developmental alterations in the hypothalamic and extra-hypothalamic regions in the HF fetal brain suggestive of a predisposition for the development of obesity and possibly neurodevelopmental abnormalities in the offspring.

  17. Molecular diagnosis of lung cancer: an overview of recent developments.

    Science.gov (United States)

    Mutti, Antonio

    2008-01-01

    Health surveillance of workers occupationally exposed to lung carcinogens calls for screening procedures which may not be fully justified, owing to current uncertainties about the outcome of early detection. Indeed, bias-free designs are difficult to set up, and the effects of lead time, length and screening biases can all result in an overestimation of the benefits of screenings, which certainly increase survival, but without any actual reduction of mortality. A major issue with modern imaging techniques is the very high incidence of discovery of lung nodules, usually false positive, but still calling for additional and sometimes painful examinations. Currently, the differential diagnosis is mainly based on additional imaging approaches, particularly positron emission tomography, which is very expensive and also shows limitations in terms of sensitivity and specificity. Therefore, purely morphological criteria seem to be insufficient to distinguish lung cancer at early stages from benign nodules with sufficient confidence. A molecular approach to the diagnosis of lung cancer through biomarkers measured by non-invasive means could greatly improve the specificity of imaging procedures. Extremely sensitive mass spectrometric techniques and polymerase chain reaction-based methods are available to detect, in accessible media, molecular alterations which characterise lung cancer at an early stage, thereby reducing the rate of false positives. The lessons learnt from decades of screening programmes based on imaging and the future prospects possibly enhanced by using biomarkers are briefly discussed in this overview. (www.actabiomedica.it)

  18. Stem cell and lung cancer development: blaming the Wnt, Hh and Notch signalling pathway.

    Science.gov (United States)

    García Campelo, María Rosario; Alonso Curbera, Guillermo; Aparicio Gallego, Guadalupe; Grande Pulido, Enrique; Antón Aparicio, Luis Miguel

    2011-02-01

    Primary lung cancer may arise from the central (bronchial) or peripheral (bronchiolo-alveolar) compartments. However the origins of the different histological types of primary lung cancer are not well understood. Stem cells are believed to be crucial players in tumour development and there is much interest in identifying those compartments that harbour stem cells involved in lung cancer. Although the role of stem cells in carcinogenesis is not well characterised, emerging evidence is providing new insights into this process. Numerous studies have indicated that lung cancer is not a result of a sudden transforming event but a multistep process in which a sequence of molecular changes result in genetic and morphological aberrations. The exact sequence of molecular events involved in lung carcinogenesis is not yet well understood, therefore deeper knowledge of the aberrant stem cell fate signalling pathway could be crucial in the development of new drugs against the advanced setting.

  19. 牦牛胎儿肺脏发育的形态学研究%Morphological study on the lung of the fetal yak

    Institute of Scientific and Technical Information of China (English)

    杨琨; 余四九; 何俊峰; 崔燕

    2012-01-01

    Lung tissue from 40 yak fetuses of different age groups were collected to investigate their development process u-sing histological and histochemical methods. The aim is to provide morphological data on developmental biology and find the hypoxia adaptive structure of the lung in yak fetus. The results showed that the developmental period of yak lung can be divided into five stages. (1) Embryologic stage (30-50 days) : a lung bud was found. Its branches formed into the primary bronchi, and then into the lobar bronchus. The bud had the pseudostratified columnar epithelium. (2) Pseudoglandular stage (50-120 days) : the bronchial tree clearly developed and its terminal bud shaped like the gland. The bud possessed the pseudostratified columnar epithelium. (3) Canalicular stage (120-180 days) ; the respiratory region has rapidly grown, no glandular structure is found in terminal buds. There were many tubular branches with the single-walled columnar epithelium or cuboid epithelium. (4) Saccular stage (180 -220 days) : terminal sac (original alveolar) was formed by the ridge of dissepiment, and a few primitive alveoli epithelia differentiated into flat type Ⅰ alveolar cells and cubical type Ⅱ alveolar cells. (5) Alveolar stage (220 -260 days) ; the alveolus was formed. Much of the epithelium differentiated into flat type I alveolar cells and cubical type Ⅱ alveolar cells. We concluded from the present study that the epithelium of bronchial and terminal buds were full of glycogen in the Embryologic stage and the Pseudoglandular stage, and beginning from the Canalicular stage, the glycogen declined sharply. Several epithelium cells in the air conductivity portion were positive for PAS in the later stages. The developmental process of lung in yak fetuses is similar to that in cattle, although the yak has a longer saccular stage and a shorter alveolar stage. The results suggest that the lung of yak fetus matures even earlier than that of cattle.%本实验选取40份不

  20. Development of a novel lung-stabilizing device for VATS procedures.

    Science.gov (United States)

    Muranishi, Yusuke; Sato, Toshihiko; Yutaka, Yojiro; Sakaguchi, Yasuto; Komatsu, Teruya; Yoshizawa, Akihiko; Hirata, Masahiro; Nakamura, Tatsuo; Date, Hiroshi

    2017-03-08

    The use of video-assisted thoracoscopic surgery (VATS) has substantially increased in recent years. These procedures involve the insertion of specialized devices into the thoracic cavity via access ports. However, conventional devices such as cotton-tipped applicators and graspers can limit the field of view and injure the fragile lung tissue. The aim of this study was to develop a novel lung-stabilizing device for VATS that provides a good surgical field of view without causing lung injury. We developed a novel suction-based lung-stabilizing device equipped with three hemispheric 20-mm-diameter silicon suction cups. The utility and safety of the novel device were evaluated using a resected pig lung and canine models. In order to assess potential organ damage arising from the use of the novel device, canine lung parenchyma and pleura were macroscopically and microscopically examined after the device had been continuously applied under negative pressure conditions of -400 or -540 mmHg for 1 h. To assess the utility of the novel device, we performed lobectomies in the resected pig lung and VATS in canine models. The device demonstrated sufficient power to stabilize the lungs and provided a clear field of view during surgery, which enabled us to perform VATS lobectomies more easily than conventional stabilizing forceps. Assessment of the dogs' lungs immediately after detaching the suction-based device revealed no complications such as hemorrhage, air leaks, and bullae formation. Pathological examination after 7 days also showed no substantial damage, except for a small impression in the parenchyma and pleura of the surface layer where the device had contacted the lung tissue. Although further validation studies in clinical settings are required, our study indicates that the novel lung-stabilizing device has potentially useful applications in VATS procedures.

  1. Ultrasonographic diagnosis and clinical prognosis of fetal congenital diseases of the lung%胎儿肺部病变产前超声表现与临床预后

    Institute of Scientific and Technical Information of China (English)

    姜小力; 邓学东; 凌晨; 唐亚奇; 梁泓

    2012-01-01

    Objective To explore the diagnostic value of ultrasonography of fetal congenital disease of the lung, and to predict the prognosis according to ultrasonographic findings . Methods A total of 49 cases of fetal congenital disease of the lung were confirmed by odinopoeia or follow -up, and the data was retrospectively analyzed. Results Among the 49 fetuses of congenital lung disease , there were 21 cases (42.9% ,21/49) of congenital cystic adenomatoid malformation ( CCAM ) , 12 cases (24. 5% , 12/49) of pulmonary sequestration ( PS) , 9 cases (18. 4% , 9/49 ) of congenital diaphragmatic hernia ( CDH) , 5 cases (10. 2% , 5/49 ) of pleural effusion ( PE ) , and 2 cases (4. 1 % , 2/49 ) of pulmonary agenesis ( PA). In ultrasonographic images , CCAM demonstrated mixed echoes with several different sizes of anechoic areas or enhanced echogenic masses in the fetal lung ;PS demonstrated wedge-shaped mass of homogeneous enhanced echo in the fetal chest; CDH demonstrated the abdominal organs pushed into the chest cavity ; PE demonstrated an echo -free zone in the intrathoracic; PA demonstrated the lobe missing. CCAM was pathologically confirmed in 15 fetuses after induced abortion ,one neonatal died ,but CCAM in other 5 fetuses disappeared before 37 weeks. PS was pathologically confirmed in 3 fetus after induced abortion , and was confirmed by MRI or pathologic examination in 6 live births , while PS in other 3 fetuses disappeared before 36 weeks. Among the 9 cases of CDH,7 fetuses were performed induced abortion (one combined with Trisomy 18) ,one live birth was survived after post -natal surgery, and one neonatal died. 4 cases of the 5 PE fetuses were performed induced abortion (combined with Trisomy 21,fetal hydrops ,Turner's syndrome and peritoneal effusion respectively) , while PE in the other one disappeared before 34 weeks. 2 cases of PA were performed induced abortion (one without the left lung , and the other without the right lung ). Conclusions Ultrasound

  2. Mechanisms for split localization of Fgf10 expression in early lung development.

    Science.gov (United States)

    Hirashima, Tsuyoshi; Iwasa, Yoh; Morishita, Yoshihiro

    2009-11-01

    In early lung development, epithelial tubes (lung buds) intrude into mesenchyme covered with pleural cells (lung border), and form tree-like networks, by means of repeated use of morphogenetic processes: "elongation," "terminal bifurcation," and "lateral budding." When a bud is elongating, a peak of Fgf10 expression is formed in the mesenchyme near the tip; whereas when terminal bifurcation and lateral budding occur, two separate peaks are formed instead. To explain the spatial pattern of Fgf10 expression, we developed a mathematical model for the regulation of Fgf10 expression with geometrical conditions including shapes of the lung buds and the lung border. Different localization patterns of Fgf10 expression can be explained by the geometrical conditions. Fgf10 expression has a single peak when a length between the tip of lung bud and the lung border is large. When the length is small, Fgf10 expression has two peaks, whose location depends on the curvature of lung border. Copyright 2009 Wiley-Liss, Inc.

  3. Fetal, neonatal, infant, and child international growth standards: an unprecedented opportunity for an integrated approach to assess growth and development.

    Science.gov (United States)

    Garza, Cutberto

    2015-07-01

    The recent publication of fetal growth and gestational age-specific growth standards by the International Fetal and Newborn Growth Consortium for the 21st Century Project and the previous publication by the WHO of infant and young child growth standards based on the WHO Multicentre Growth Reference Study enable evaluations of growth from ∼9 wk gestation to 5 y. The most important features of these projects are the prescriptive approach used for subject selection and the rigorous testing of the assertion that growth is very similar among geographically and ethnically diverse nonisolated populations when health, nutrition, and other care needs are met and the environment imposes minimal constraints on growth. Both studies documented that with adequate controls, the principal source of variability in growth during gestation and early childhood resides among individuals. Study sites contributed much less to observed variability. The agreement between anthropometric measurements common to both studies also is noteworthy. Jointly, these studies provide for the first time, to my knowledge, a conceptually consistent basis for worldwide and localized assessments and comparisons of growth performance in early life. This is an important contribution to improving the health care of children across key periods of growth and development, especially given the appropriate interest in pursuing "optimal" health in the "first 1000 d," i.e., the period covering fertilization/implantation, gestation, and postnatal life to 2 y of age. © 2015 American Society for Nutrition.

  4. Bi-iliac distance and iliac bone position compared to the vertebral column in normal fetal development.

    Science.gov (United States)

    Hartling, U B; Fischer Hansen, B; Skovgaard, L T; Kjaer, I

    2001-03-01

    Prenatal standards of bi-iliac width were not found in the literature based on autopsy investigations, nor was the caudo-cranial position of the ilia compared to the vertebral column. The first purpose of the present study was to establish normal standard values for the bi-iliac distance in fetal life, the second to evaluate the level of the iliac bones proportional to the ossified vertebral column. Whole body radiographs in antero-posterior projections from 98 human fetuses (36 female and 44 male fetuses, as well as 18 fetuses on which the sex had not been determined) were analyzed in the study. The fetuses derived from spontaneous or induced abortions and they were radiographed as part of the required autopsy procedure. The crown-rump-length (CRL) of the fetuses varied from 32 to 245 mm. The outer and inner bi-iliac distance was measured from the radiographs with a digital Helios slide caliper. The caudo-cranial position of the iliac bones was evaluated. The present study shows that in normal fetal development there is a continuous linear enlargement of the pelvic region in the transverse and vertical planes. The upper iliac contour stays at the level of the first sacral vertebral body, whereas the lower iliac line moves caudally. Significant differences between male and female fetuses were not found. The value of the present study is that the results can be used as reference standards in prenatal pathology. Copyright 2001 Wiley-Liss, Inc.

  5. Hypoplastic left heart syndrome and the nutmeg lung pattern in utero: a cause and effect relationship or prognostic indicator?

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    Saul, David; Johnson, Ann M.; Victoria, Teresa [The Children' s Hospital of Philadelphia, Radiology Department, Philadelphia, PA (United States); Degenhardt, Karl; Rychik, Jack [The Children' s Hospital of Philadelphia, Cardiac Center and Fetal Heart Program, Philadelphia, PA (United States); Iyoob, Suzanne D.; Johnson, Mark P. [The Children' s Hospital of Philadelphia, Center for Fetal Diagnosis and Treatment, Philadelphia, PA (United States); Surrey, Lea F. [The Children' s Hospital of Philadelphia, Pathology Department, Philadelphia, PA (United States)

    2016-04-15

    Hypoplastic left heart syndrome (HLHS) is the third most common cause of critical congenital heart disease in newborns, and one of the most challenging forms to treat. Secondary pulmonary lymphangiectasia has been recognized in association with HLHS, an appearance described on fetal MRI as the ''nutmeg lung.'' To investigate the association of fetal nutmeg lung with HLHS survival. A retrospective search of the fetal MRI database was performed. The nutmeg lung pattern was defined as T2 heterogeneous signal with tubular structures radiating peripherally from the hila. Postnatal echocardiograms and charts were reviewed. Forty-four fetal MR studies met inclusion criteria, of which 4 patients (9%) had the nutmeg lung pattern and 3 of whom also had restrictive lesions. Mortality in this nutmeg lung group was 100% by 5 months of age. Of the 40 patients without nutmeg lung, mortality/orthotopic heart transplant (OHT) was 35%. Of these 40 patients without nutmeg lung, 5 had restriction on echo, 3 of whom died/had OHT before 5 months of age (60% of patients with restriction and non-nutmeg lung). There was a significantly higher incidence of restrictive lesions (P = 0.02) and mortality/OHT (P = 0.02) in patients with nutmeg lung compared to those without. The nutmeg lung MR appearance in HLHS fetuses is associated with increased mortality/OHT (100% in the first 5 months of life compared to 35% with HLHS alone). Not all patients with restrictive lesions develop nutmeg lung, and outcome is not as poor when restriction is present in isolation. Dedicated evaluation for nutmeg lung pattern on fetal MR studies may be useful to guide prognostication and aid clinicians in counseling parents of fetuses with HLHS. (orig.)

  6. Ubp43 gene expression is required for normal Isg15 expression and fetal development

    Science.gov (United States)

    Rempel, Lea A; Austin, Kathleen J; Ritchie, Kenneth J; Yan, Ming; Shen, Meifeng; Zhang, Dong-Er; Henkes, Luiz E; Hansen, Thomas R

    2007-01-01

    Background Isg15 covalently modifies murine endometrial proteins in response to early pregnancy. Isg15 can also be severed from targeted proteins by a specific protease called Ubp43 (Usp18). Mice lacking Ubp43 (null) form increased conjugated Isg15 in response to interferon. The Isg15 system has not been examined in chorioallantoic placenta (CP) or mesometrial (MM) components of implantation sites beyond 9.5 days post coitum (dpc). It was hypothesized that deletion of Ubp43 would cause disregulation of Isg15 in implantation sites, and that this would affect pregnancy rates. Methods Heterozygous (het) Ubp43 mice were mated and MM and CP implantation sites were collected on 12.5 and 17.5 days post-coitum (dpc). Results Free and conjugated Isg15 were greater on 12.5 versus 17.5 dpc in MM. Free and conjugated Isg15 were also present in CP, but did not differ due to genotype on 12.5 dpc. However, null CP had greater free and conjugated Isg15 when compared to het/wt on 17.5 dpc. Null progeny died in utero with fetal genotype ratios (wt:het:null) of 2:5:1 on 12.5 and 2:2:1 on 17.5 dpc. Implantation sites were disrupted within the junctional zone and spongiotrophoblast, contained less vasculature based on lectin B4 staining and contained greater Isg15 mRNA and VEGF protein in Ubp43 null when compared to wt placenta. Conclusion It is concluded that Isg15 and its conjugates are present in implantation sites during mid to late gestation and that deletion of Ubp43 causes an increase in free and conjugated Isg15 at the feto-maternal interface. Also, under mixed genetic background, deletion of Ubp43 results in fetal death. PMID:17381847

  7. Prediction of fetal lung maturity using the lecithin/sphingomyelin (L/S) ratio analysis with a simplified sample preparation, using a commercial microtip-column combined with mass spectrometric analysis.

    Science.gov (United States)

    Kwak, Ho-Seok; Chung, Hee-Jung; Choi, Young Sik; Min, Won-Ki; Jung, So Young

    2015-07-01

    Fetal lung maturity is estimated using the lecithin/sphingomyelin ratio (L/S ratio) in amniotic fluid and it is commonly measured with thin-layer chromatography (TLC). The TLC method is time consuming and technically difficult; however, it is widely used because there is no alternative. We evaluated a novel method for measuring the L/S ratio, which involves a tip-column with a cation-exchange resin and mass spectrometry. Phospholipids in the amniotic fluid were extracted using methanol and chloroform. Choline-containing phospholipids such as lecithin and sphingomyelin were purified by passing them through the tip-column. LC-MS/MS and MALDI-TOF were used to directly analyze the purified samples. The L/S ratio by mass spectrometry was calculated from the sum peak intensity of the six lecithin, and that of sphingomyelin 34:1. In 20 samples, the L/S ratio determined with TLC was significantly correlated with that obtained by LC-MS/MS and MALDI-TOF. There was a 100% concordance between the L/S ratio by TLC and that by LC-MS/MS (kappa value=1.0). The concordance between the L/S ratio by TLC and that by MALDI-TOF was also 100% (kappa value=1.0). Our method provides a faster, simpler, and more reliable assessment of fetal lung maturity. The L/S ratio measured by LC-MS/MS and MALDI-TOF offers a compelling alternative method to traditional TLC. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Epithelial-Derived Inflammation Disrupts Elastin Assembly and Alters Saccular Stage Lung Development.

    Science.gov (United States)

    Benjamin, John T; van der Meer, Riet; Im, Amanda M; Plosa, Erin J; Zaynagetdinov, Rinat; Burman, Ankita; Havrilla, Madeline E; Gleaves, Linda A; Polosukhin, Vasiliy V; Deutsch, Gail H; Yanagisawa, Hiromi; Davidson, Jeffrey M; Prince, Lawrence S; Young, Lisa R; Blackwell, Timothy S

    2016-07-01

    The highly orchestrated interactions between the epithelium and mesenchyme required for normal lung development can be disrupted by perinatal inflammation in preterm infants, although the mechanisms are incompletely understood. We used transgenic (inhibitory κB kinase β transactivated) mice that conditionally express an activator of the NF-κB pathway in airway epithelium to investigate the impact of epithelial-derived inflammation during lung development. Epithelial NF-κB activation selectively impaired saccular stage lung development, with a phenotype comprising rapidly progressive distal airspace dilation, impaired gas exchange, and perinatal lethality. Epithelial-derived inflammation resulted in disrupted elastic fiber organization and down-regulation of elastin assembly components, including fibulins 4 and 5, lysyl oxidase like-1, and fibrillin-1. Fibulin-5 expression by saccular stage lung fibroblasts was consistently inhibited by treatment with bronchoalveolar lavage fluid from inhibitory κB kinase β transactivated mice, Escherichia coli lipopolysaccharide, or tracheal aspirates from preterm infants exposed to chorioamnionitis. Expression of a dominant NF-κB inhibitor in fibroblasts restored fibulin-5 expression after lipopolysaccharide treatment, whereas reconstitution of fibulin-5 rescued extracellular elastin assembly by saccular stage lung fibroblasts. Elastin organization was disrupted in saccular stage lungs of preterm infants exposed to systemic inflammation. Our study reveals a critical window for elastin assembly during the saccular stage that is disrupted by inflammatory signaling and could be amenable to interventions that restore elastic fiber assembly in the developing lung.

  9. Expression of SHH signaling pathway components in the developing human lung.

    Science.gov (United States)

    Zhang, Mingfeng; Wang, Hong; Teng, Hongqi; Shi, Jueping; Zhang, Yanding

    2010-10-01

    The Sonic hedgehog (Shh) cascade is crucial for the patterning of the early lung morphogenesis in mice, but its role in the developing human lung remains to be determined. In the present study, the expression patterns of SHH signaling pathway components, including SHH, PTCH1, SMO, GLI1, GLI2 and GLI3 were examined by in situ hybridization and immunohistochemistry, and compared with the equivalent patterns in mice. Our results showed that, as in mice, SHH was expressed in the epithelium of the developing human lung. However, SHH receptors (PTCH1 and SMO) and SHH signaling effectors (GLI1-3) were strongly detected in the human lung epithelium, but weakly in the mesenchyme, slightly different from their expressions in mice. Furthermore, the expression levels of SHH signaling pathway genes in human lung, but not that of GLI1, were subsequently downregulated at the canalicular stage evaluated by real-time PCR, coincident with a decline in the developing murine lung. In conclusion, in spite of slight differences, the considerable similarities of gene expression in human and mice suggest that conserved molecular networks regulate mammalian lung development.

  10. Fetal laser therapy: applications in the management of fetal pathologies.

    Science.gov (United States)

    Mathis, Jérôme; Raio, Luigi; Baud, David

    2015-07-01

    Fetoscopic coagulation of placental anastomoses is the treatment of choice for severe twin-to-twin transfusion syndrome. In the present day, fetal laser therapy is also used to treat amniotic bands, chorioangiomas, sacrococcygeal teratomas, lower urinary tract obstructions and chest masses, all of which will be reviewed in this article. Amniotic band syndrome can cause limb amputation by impairing downstream blood flow. Large chorioangiomas (>4 cm), sacrococcygeal teratomas or fetal hyperechoic lung lesions can lead to fetal compromise and hydrops by vascular steal phenomenon or compression. Renal damage, bladder dysfunction and lastly death because of pulmonary hypolasia may be the result of megacystis caused by a posterior urethral valve. The prognosis of these pathologies can be dismal, and therapy options are limited, which has brought fetal laser therapy to the forefront. Management options discussed here are laser release of amniotic bands, laser coagulation of the placental or fetal tumor feeding vessels and laser therapy by fetal cystoscopy. This review, largely based on case reports, does not intend to provide a level of evidence supporting laser therapy over other treatment options. Centralized evaluation by specialists using strict selection criteria and long-term follow-up of these rare cases are now needed to prove the value of endoscopic or ultrasound-guided laser therapy.

  11. Gravity in mammalian organ development: differentiation of cultured lung and pancreas rudiments during spaceflight

    Science.gov (United States)

    Spooner, B. S.; Hardman, P.; Paulsen, A.

    1994-01-01

    Organ culture of embryonic mouse lung and pancreas rudiments has been used to investigate development and differentiation, and to assess the effects of microgravity on culture differentiation, during orbital spaceflight of the shuttle Endeavour (mission STS-54). Lung rudiments continue to grow and branch during spaceflight, an initial result that should allow future detailed study of lung morphogenesis in microgravity. Cultured embryonic pancreas undergoes characteristic exocrine acinar tissue and endocrine islet tissue differentiation during spaceflight, and in ground controls. The rudiments developing in the microgravity environment of spaceflight appear to grow larger than their ground counterparts, and they may have differentiated more rapidly than controls, as judged by exocrine zymogen granule presence.

  12. Stimulatory Effects of Coumestrol on Embryonic and Fetal Development Through AKT and ERK1/2 MAPK Signal Transduction.

    Science.gov (United States)

    Lim, Whasun; Song, Gwonhwa

    2016-12-01

    Successful establishment of pregnancy is required for fetal-maternal interactions regulating implantation, embryonic development and placentation. A uterine environment with insufficient growth factors and nutrients increases the incidence of intrauterine growth restriction (IUGR) leading to an impaired uterine environment. In the present study, we demonstrated the effects of the phytoestrogen coumestrol on conceptus development in the pig that is regarded as an excellent biomedical animal model for research on IUGR. Results of this study indicated that coumestrol induced migration of porcine trophectoderm (pTr) cells in a concentration-dependent manner. In response to coumestrol, the phosphorylation of AKT, P70S6K, S6, ERK1/2 MAPK, and P90RSK proteins were activated in pTr cells and ERK1/2 MAPK and P90RSK phosphorylation was prolonged for a longer period than for the other proteins. To identify the signal transduction pathway induced by coumestrol, pharmacological inhibitors U0126 (an ERK1/2 inhibitor) and LY294002 (a PI3K inhibitor) were used to pretreat pTr cells. The results showed that coumestrol-induced phosphorylation of ERK1/2 MAPK and P90RSK was blocked by U0126. In addition, the increased phosphorylation in response to coumestrol was completely inhibited following pre-treatment incubation of pTr cells in the presence of LY294002 and U0126. Furthermore, these two inhibitors suppressed the ability of coumestrol to induce migration of pTr cells. Collectively, these findings suggest that coumestrol affects embryonic development through activation of the PI3K/AKT and ERK1/2 MAPK cell signal transduction pathways and improvement in the uterine environment through coumestrol supplementation may provide beneficial effects of enhancing embryonic and fetal survival and development. J. Cell. Physiol. 231: 2733-2740, 2016. © 2016 Wiley Periodicals, Inc.

  13. Low Level Laser Therapy Reduces the Development of Lung Inflammation Induced by Formaldehyde Exposure.

    Directory of Open Access Journals (Sweden)

    Cristiane Miranda da Silva

    Full Text Available Lung diseases constitute an important public health problem and its growing level of concern has led to efforts for the development of new therapies, particularly for the control of lung inflammation. Low Level Laser Therapy (LLLT has been highlighted as a non-invasive therapy with few side effects, but its mechanisms need to be better understood and explored. Considering that pollution causes several harmful effects on human health, including lung inflammation, in this study, we have used formaldehyde (FA, an environmental and occupational pollutant, for the induction of neutrophilic lung inflammation. Our objective was to investigate the local and systemic effects of LLLT after FA exposure. Male Wistar rats were exposed to FA (1% or vehicle (distillated water during 3 consecutive days and treated or not with LLLT (1 and 5 hours after each FA exposure. Non-manipulated rats were used as control. 24 h after the last FA exposure, we analyzed the local and systemic effects of LLLT. The treatment with LLLT reduced the development of neutrophilic lung inflammation induced by FA, as observed by the reduced number of leukocytes, mast cells degranulated, and a decreased myeloperoxidase activity in the lung. Moreover, LLLT also reduced the microvascular lung permeability in the parenchyma and the intrapulmonary bronchi. Alterations on the profile of inflammatory cytokines were evidenced by the reduced levels of IL-6 and TNF-α and the elevated levels of IL-10 in the lung. Together, our results showed that LLLT abolishes FA-induced neutrophilic lung inflammation by a reduction of the inflammatory cytokines and mast cell degranulation. This study may provide important information about the mechanisms of LLLT in lung inflammation induced by a pollutant.

  14. Acurácia do teste de Clements para avaliação da maturidade pulmonar fetal em gestantes com doença hipertensiva específica da gestação Accuracy of Clements' test for evaluation of fetal lung maturation in preeclamptic patients

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    Melania Maria Ramos de Amorim

    1998-06-01

    -negativos foram freqüentes, em torno de 40% para os resultados negativos/intermediários. Conclusões: o teste de Clements representa um bom teste para investigação maturação pulmonar fetal em casos de DHEG, sendo raros os resultados falso-positivos. No entanto, em virtude da especificidade baixa, com elevada freqüência de resultados falso-negativos, seus resultados devem ser analisados com cautela, complementando-se a pesquisa de maturidade com outros métodos (sobretudo em casos graves, quando a maturidade pulmonar presente irá determinar a indicação de interrupção da gestação.Objectives: To determine sensitivity, specificity, positive and negative predictive values of the shake test (Clements for evaluation of fetal lung maturation in preeclamptic patients. Methods: A prospective study for validation of a diagnostic method was conducted enrolling 163 preeclamptic patients (gestational age between 28-34 weeks admitted at CAM-IMIP with indication for fetal maturity testing. Preeclampsia diagnosis and classification followed criteria of the National High Blood Pressure Working Group, 1990. Clements' test was performed in three tubes and positive, negative or intermediate results were considered for analysis (related to presence or absence of fetal lung maturity. Accuracy parameters were calculated considering actual incidence of hyaline membrane disease (positive maturity = absent disease after birth. Hyaline membrane disease was defined by criteria of CLAP, 1978. Statistical analysis was performed using c² test (Epi-Info 6.04b with a 5% significance level. Results: Intermediate results were considered alternately as positive or negative for analysis. When considered positive, sensitivity was 87.9% and specificity 74.5% with positive and negative predictive values of 8.9.4% and 71.4% respectively - efficiency was 84%. When intermediate results were evaluated as negative, sensitivity decreased to 62% and specificity raised to 89.4% and positive and negative

  15. Avaliação da maturidade pulmonar fetal pela contagem dos corpos lamelares no líquido amniótico Evaluation of fetal lung maturity by lamellar bodies counting in amniotic fluid

    Directory of Open Access Journals (Sweden)

    Beatriz Maykot Kuerten Gil

    2010-03-01

    Full Text Available OBJETIVO: comparar o teste de contagem de corpos lamelares (CCL no líquido amniótico com o teste da polarização fluorescente (PF como parâmetro diagnóstico para avaliação da maturidade pulmonar fetal. MÉTODO: estudo transversal, analítico e controlado realizado com 60 gestantes atendidas no período de março de 2002 a dezembro de 2007. Foram colhidas amostras de líquido amniótico e realizados os testes de CCL e PF (TDxFLM II, considerados de referência, e comparados à presença ou ausência da Síndrome do Desconforto Respiratório (SDR. Foram estabelecidos valores de corte para maturidade de 30 mil corpos lamelares/µL para o teste da CCL e 55 mg/g de albumina para o PF. Foram avaliadas as características maternas e perinatais, a evolução neonatal e o desempenho dos testes diagnósticos para predição da maturidade pulmonar fetal. Na análise estatística, foram utilizadas medidas descritivas e calculados os valores referentes à sensibilidade, especificidade, valor preditivo positivo e negativo dos testes, considerando-se significativos valores de pPURPOSE: to compare the lamellar body number density (LBND count in amniotic fluid using the fluorescent polarization (FP test as a diagnostic parameter for the assessment of fetal pulmonary maturity. METHOD: this was an analytical, controlled cross-sectional study conducted on 60 pregnant women from March 2002 to December 2007. Amniotic fluid specimens were obtained by amniocentesis or at the time of caesarean section, and submitted to the LBND and FP tests (TDxFLM®, Abbott Laboratories, the latter considered to be a reference test, and compared in terms of the presence or absence of respiratory distress syndrome (RDS. Cut-off values for maturity were established at 30,000 lamellar bodies/µL for the LBND test and 55 mg/g albumin for the FP test. Maternal and perinatal characteristics and neonatal evolution were evaluated, and the performance of the diagnostic tests regarding

  16. Maternal exposure to diphenhydramine during the fetal period in rats: effects on physical and neurobehavioral development and on neurochemical parameters.

    Science.gov (United States)

    Moraes, A P; Schwarz, A; Spinosa, H S; Florio, J C; Bernardi, M M

    2004-01-01

    Previous research from our laboratory suggested that the administration of antihistaminics (H(1) receptor antagonists) to pregnant Wistar rats throughout pregnancy altered brain sexual differentiation and dopaminergic physiology of the offspring. In the present study, we assessed the effects of 20 mg/kg diphenhydramine (DPH) administration to pregnant rats during the fetal period of pregnancy [Gestation Days (GDs) 16-21], a critical period for brain sexual differentiation and central nervous system (CNS) maturation. Maternal body weight and water and food consumption were measured during pregnancy and offspring physical and behavioral development were evaluated during lactation. Offspring open-field behavior was assessed at 21 and 100 days of age. After the final open-field test, male and female sexual behavior, stereotypy following an apomorphine challenge, striatal content of dopamine (DA), the dopamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA), serotonin (5-HT) and the serotonin metabolite 5-hydroxyindolacetic acid (5-HIAA) were assessed. There were no significant treatment-related changes in maternal reproductive parameters, but DPH treatment decreased maternal body weight gain during the treatment period. Offspring physical parameters were not altered in the treated group, and no significant treatment-related changes were found in female open-field measures, sexual behavior or in striatal neurochemical measurements. However, delayed testis descent and altered patterns of sexual behavior occurred in male offspring accompanied by increased striatal DA, decreased striatal DOPAC as well as reduced DOPAC/DA, HVA/DA and 5-HIAA/5-HT ratios. Taken together, these data suggest that exposure to DPH during the fetal period of rat development altered postnatal CNS maturation and sexual development of male offspring via changes in striatal bioamine systems.

  17. Region-specific growth effects in the developing rat prostate following fetal exposure to estrogenic ultraviolet filters.

    Science.gov (United States)

    Hofkamp, Luke; Bradley, Sarahann; Tresguerres, Jesus; Lichtensteiger, Walter; Schlumpf, Margret; Timms, Barry

    2008-07-01

    Exposure to environmental endocrine disruptors is a potential risk factor for humans. Many of these chemicals have been shown to exhibit disruption of normal cellular and developmental processes in animal models. Ultraviolet (UV) filters used as sunscreens in cosmetics have previously been shown to exhibit estrogenic activity in in vitro and in vivo assays. We examined the effects of two UV filters, 4-methylbenzylidene camphor (4-MBC) and 3-benzylidene camphor (3-BC), in the developing prostate of the fetal rat. Pregnant Long Evans rats were fed diets containing doses of 4-MBC and 3-BC that resulted in average daily intakes of these chemicals corresponding to the lowest observed adverse effects level (LOAEL) and the no observed adverse effects level (NOAEL) doses in prior developmental toxicity studies. Using digital photographs of serial sections from postnatal day 1 animals, we identified, contoured, and aligned the epithelial ducts from specific regions of the developing prostate, plus the accessory sex glands and calculated the total volume for each region from three-dimensional, surface-rendered models. Fetal exposure to 4-MBC (7.0 mg/kg body weight/day) resulted in a significant increase (p < 0.05) in tissue volume in the prostate and accessory sex glands. Treated males exhibited a 62% increase in the number of ducts in the caudal dorsal prostate. Increased distal branching morphogenesis appears to be a consequence of exposure in the ventral region, resulting in a 106% increase in ductal volume. 4-MBC exposure during development of the male reproductive accessory sex glands exhibited classical growth effects associated with estrogenic endocrine disruptors. The different regional responses suggest that the two developmental processes of ductal outgrowth and branching morphogenesis are affected independently by exposure to the environmental chemicals.

  18. Restrictive dermopathy and fetal behaviour

    NARCIS (Netherlands)

    Mulder, EJH; Beemer, FA; Stoutenbeek, P

    2001-01-01

    We report three siblings from consecutive pregnancies affected with restrictive dermopathy (RD). During the second pregnancy, fetal behavioural development and growth were studied extensively using ultrasound at 1-4 week intervals. Dramatic and sudden changes occurred in fetal body movements and gro

  19. Development of DARPP-32-positive parts of fetal pig ganglionic eminence and ventral mesencephalon in organotypic slice co-cultures

    DEFF Research Database (Denmark)

    Dall, Annette Møller; Rasmussen, Jens Zimmer

    2006-01-01

    Neurons from the fetal pig dopaminergic ventral mesencephalon (VM) and basal ganglia anlage (the ganglionic eminence) were co-cultured as organotypic slice cultures to study the development of the two interconnected brain areas. During a short developmental period (E35-E42), a groove separates th...... esterase (AChE) and were the preferred target areas for TH-positive fibers from the co-cultured VM....... (TH)-positive, dopaminergic fibers from co-cultured slices of the ventral mesencephalon. DARPP-32 expression was more extensive and dense in cultures of the lateral part of the striatal anlage than the medial part. The DARPP-32-positive areas moreover overlapped with areas rich in acetylcholine...

  20. Development of a new interfacility extracorporeal membrane oxygenation transport program for pediatric lung transplantation evaluation

    Science.gov (United States)

    Shepherd, Edward G.; Gee, Samantha W.

    2017-01-01

    Pediatric lung transplantation is a life-saving intervention for children with irreversible end-stage lung disease. Access to transplant can be limited by geographic isolation from a center or the presence of comorbidities affecting transplant eligibility. Extracorporeal membrane oxygenation (ECMO)-supported patients are an uncommon but historically high-risk cohort of patients considered for lung transplant. We report the development of a service at our center to provide transport services to our hospital for patients unable to wean from ECMO support at their local institution for the purpose of evaluation for lung transplantation by our program. We developed a process for pre-transport consultation by the lung transplant physician team, standardized hand-off tools and equipment lists, and procedures for transitioning patients to transport ECMO machinery. Four patients have been transported to date including fixed wing (FW) and helicopter transports. All patients were successfully transported with either none or minor complications. Transport of ECMO-supported patients is a feasible method to increase access of patients with irreversible lung injured patients to evaluation for lung transplant. PMID:28275613

  1. Fate and Development of Human Vomeronasal Organ - A Microscopic Fetal Study.

    Science.gov (United States)

    Vasuki, A K Manicka; Fenn, T K Aleyemma; Devi, M Nirmala; Hebzibah, T Deborah Joy; Jamuna, M; Sundaram, K Kalyana

    2016-03-01

    The existence of Vomeronasal organ in human is a controversial subject. Presence of Vomeronasal organ and its structure was not reported in standard text books. The presence of Vomeronasal organ in fetal life is doubtful. Hence identification of the organ by histological examination was planned. A study was conducted on resected specimens of nasal septum obtained from 45 spontaneously aborted fetuses from Obstetrics and Gynaecology department, PSG Institute of Medical Sciences and Research, Coimbatore, after ethical clearance. The histological structure of Vomeronasal organ was observed from 11 weeks old fetus. The epithelial lining of the organ, presence of cilia, presence of lamina propria, acini and the blood vessel and the types of cells were observed. The organ was lined by pseudostratified columnar epithelium. The organ showed Lamina propria with serous acini from 18 weeks fetus. Vomeronasal duct opening into the nasal cavity and three types of cells were observed in 28 weeks fetus. Knowledge about the persistence of Vomeronasal organ in fetuses and its structure need to be known. The organ may be found as a putative pit posterior to anterior nasal spine. The organ may be damaged in nasal septal surgeries and nasal endoscopic procedures. The organ may not be seen on gross examination in all human fetuses and cadavers.

  2. Cell therapy of pain: Characterization of human fetal chromaffin cells at early adrenal medulla development.

    Science.gov (United States)

    Zhou, H; Aziza, J; Sol, J C; Courtade-Saïdi, M; Chatelin, S; Evra, C; Parant, O; Lazorthes, Y; Jozan, S

    2006-04-01

    Adult adrenal chromaffin cells are being utilized for therapeutic transplantation. With the prospect of using fetal chromaffin cells in pain therapy, we studied their phenotype, proliferative power, function, and growth in vitro and in situ in order to determine the optimal time for implantation. Between 7 and 10 gestational weeks (GW), we isolated, in vitro, two types of chromaffin cells with a noradrenergic phenotype akin to that observed, in situ. Among the adherent chromaffin cells first observed in vitro, only a few samples expressed met-enkephalin, whereas almost all the neurosphere-like colonies, which appeared later, expressed it. However, neither of the two types of populations expressed an adrenergic phenotype in line with that observed in situ. At the upper limits of the voluntary abortion period authorized in France, this phenotype (12 GW) and met-enkephalin expression (13 GW) were evidenced in situ. For the first time in man, we demonstrate the secretion of noradrenaline in vitro by the two populations of cells. Consistent with this result, we also noted dopamine beta hydroxylase (DbetaH) mRNA expression in vitro and in situ within this period. These observations on the expression of these biological factors indicate that 9-10 GW would be the best stage for sampling these cells for preclinical transplantation experiments.

  3. Development of an artificial neuronal network with post-mitotic rat fetal hippocampal cells by polyethylenimine.

    Science.gov (United States)

    Liu, Bingfang; Ma, Jun; Gao, Erjing; He, Yu; Cui, Fuzhai; Xu, Qunyuan

    2008-03-14

    The selection of appropriate surface materials that promote cellular adhesion and growth is an important consideration when designing a simplified neuronal network in vitro. In the past, extracellular matrix proteins such as laminin (LN) or positively charged substances such as poly-l-lysine (PLL) have been used. In this study, we examined the ability of another positively charged polymer, polyethyleneimine (PEI), to promote neuronal adhesion, growth and the formation of a functional neuronal network in vitro. PEI, PLL and LN were used to produce grid-shape patterns on glass coverslips by micro-contact printing. Post-mitotic neurons from the rat fetal hippocampus were cultured on the different polymers and the viability and morphology of these neurons under serum-free culture conditions were observed using fluorescent microscopy and atomic force microscopy (AFM). We show that neurons cultured on the PEI- and PLL-coated surfaces adhered to and extended neurites along the grid-shape patterns, whereas neurons cultured on the LN-coated coverslips clustered into clumps of cells. In addition, we found that the neurons on the PEI and PLL-coated grids survived for more than 2 weeks in serum-free conditions, whereas most neurons cultured on the LN-coated grids died after 1 week. Using AFM, we observed some neurosynapse-like structures near the neuronal soma on PEI-coated coverslips. These findings indicate that PEI is a suitable surface for establishing a functional neuronal network in vitro.

  4. [The theory of mechanical activity of lungs--a creation history, the present and development prospects].

    Science.gov (United States)

    Tetenev, F F; Tetenev, K F

    2014-01-01

    In article the history of creation of the doctrine about respiratory movements of lungs, history of classical mechanics of breathing is stated. Supervision of the paradoxical facts which became a basis for hypothesis creation, then the theory of mechanical activity of lungs are presented. The facts proving mechanical activity of lungs on an inspiration and an expiration are given. Options of interaction of intra pulmonary and extra pulmonary sources of mechanical energy are considered. Theoretical justification for development of the new direction of studying of physiology of mechanical movements of the internal which does not have own skeleton is stated.

  5. Magnesium and fetal growth

    Energy Technology Data Exchange (ETDEWEB)

    Weaver, K.

    1988-01-01

    Fetal growth retardation and premature labor are major problems in perinatal medicine today and account for a great deal of the observed fetal morbidity. While the neonatal death rate has steadily declined over the past decade, there has been a lack of concommitant decrease in these two leading problems. Magnesium (Mg/sup ++/) plays a major role in both of these areas of concern. The fact that it is used as a treatment for premature labor has led investigators to look at low Mg/sup ++/ as a possible cause of this poorly understood phenomenon. The second major cause of small for gestational age infants is intrauterine growth retardation, a condition which may be of either fetal or maternal origin. In either case, Mg/sup ++/ may be implicated since it exerts a strong influence on the underlying pathophysiology of placental failure and maternal hypertension. Both of these conditions are mediated by vascular and platelet hyperactivity as well as by and increase in the ration of thromboxane to prostacyclin. Studies in both the human and animal species are beginning to show how Mg/sup ++/ interacts in these conditions to produce such a damaging fetal outcome. The recent use of Doppler velocimetry of the developing fetus has shown reduced fetal vascular and maternal uterine vascular compliance as early as 14 weeks of gestation in those who would be so affected.

  6. Fetal pain

    NARCIS (Netherlands)

    Adama van Scheltema, Phebe

    2011-01-01

    Recent studies have suggested that the fetus is capable of exhibiting a stress response to intrauterine needling, resulting in alterations in fetal stress hormone levels. Intrauterine transfusions are performed by inserting a needle either in the umbilical cord root at the placental surface (PCI), o

  7. Fetal cell microchimerism develops through the migration of fetus-derived cells to the maternal organs early after implantation.

    Science.gov (United States)

    Sunami, Rei; Komuro, Mayuko; Yuminamochi, Tsutomu; Hoshi, Kazuhiko; Hirata, Shuji

    2010-03-01

    Fetus-derived cells are present in the blood and tissues of the maternal body over a long period of time, even after delivery, resulting in fetal cell microchimerism. The exact process by which fetal cells cross the placental barrier to enter the maternal circulation is unclear. The objective of this paper was to determine the time during pregnancy that fetal cells with multilineage potential migrate to the maternal organs. Wild type female mice were crossbred with male transgenic mice, expressing enhanced green fluorescent protein (EGFP). Total hysterectomies were performed at different time points of pregnancy. On day 60 after surgery, mice were injected with either streptozotocin (STZ) to induce insulin-dependent diabetes mellitus, or vehicle. Detection and quantification of fetal cells were then undertaken in a variety of maternal organs via fluorescent microscopy and quantitative PCR amplification of the gfp transgene. In vehicle control mice, fetal cells were detected only in the maternal bone marrow. However on day 30 after STZ injection, fetal cells were detected not only in bone marrow but also in the maternal pancreas, liver and kidney. Histological analysis showed differentiated fetal cells within the pancreatic acinar cells, hepatocytes and tubular epithelial cells. Their morphological appearance was indistinguishable from their maternal counterparts, and their frequency in these organs was constant, regardless of the timing of hysterectomy. These results indicate that most fetal cells with multilineage potential in maternal tissues migrate to the maternal body early after implantation, and thereafter sustain their population over the long term after delivery.

  8. Platform dependence of inference on gene-wise and gene-set involvement in human lung development

    Directory of Open Access Journals (Sweden)

    Kho Alvin T

    2009-06-01

    Full Text Available Abstract Background With the recent development of microarray technologies, the comparability of gene expression data obtained from different platforms poses an important problem. We evaluated two widely used platforms, Affymetrix U133 Plus 2.0 and the Illumina HumanRef-8 v2 Expression Bead Chips, for comparability in a biological system in which changes may be subtle, namely fetal lung t