WorldWideScience

Sample records for abnormal placental development

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

    Keisuke Nagao

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

  2. Markers of placental insufficiency: etiology and the risk of cerebral palsy:Population based studies of preeclampsia, low birth weight, and abnormal placental weight

    Strand, Kristin Melheim

    2015-01-01

    Placental insufficiency may be defined as a placenta not able to perform its central tasks; namely, delivery of sufficient oxygen and nutrients to the developing fetus. In this thesis, preeclampsia, fetal growth restriction (FGR), and abnormal placental weight were applied as markers of placental insufficiency. Abnormal interaction between fetal and maternal tissues during placentation, leading to shallow placentation, may be the commencing step of placental insufficiency. C...

  3. A stochastic model for early placental development.

    Cotter, Simon L

    2014-08-01

    In the human, placental structure is closely related to placental function and consequent pregnancy outcome. Studies have noted abnormal placental shape in small-for-gestational-age infants which extends to increased lifetime risk of cardiovascular disease. The origins and determinants of placental shape are incompletely understood and are difficult to study in vivo. In this paper, we model the early development of the human placenta, based on the hypothesis that this is driven by a chemoattractant effect emanating from proximal spiral arteries in the decidua. We derive and explore a two-dimensional stochastic model, and investigate the effects of loss of spiral arteries in regions near to the cord insertion on the shape of the placenta. This model demonstrates that disruption of spiral arteries can exert profound effects on placental shape, particularly if this is close to the cord insertion. Thus, placental shape reflects the underlying maternal vascular bed. Abnormal placental shape may reflect an abnormal uterine environment, predisposing to pregnancy complications. Through statistical analysis of model placentas, we are able to characterize the probability that a given placenta grew in a disrupted environment, and even able to distinguish between different disruptions.

  4. Pathophysiology of placentation abnormalities in pregnancy-induced hypertension

    Mitsuko Furuya

    2008-11-01

    Full Text Available Mitsuko Furuya1, Junji Ishida2,3, Ichiro Aoki1, Akiyoshi Fukamizu2,31Department of Pathology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan; 2Graduate School of Life and Environmental Sciences; 3Center for Tsukuba Advanced Research Alliance (TARA, University of Tsukuba, Tsukuba 305-8577, JapanAbstract: During embryogenesis and development, the fetus obtains oxygen and nutrients from the mother through placental microcirculation. The placenta is a distinctive organ that develops and differentiates per se, and that organizes fetal growth and maternal condition in the entire course of gestation. Several life-threatening diseases during pregnancy, such as pregnancy-induced hypertension (PIH and eclampsia, are closely associated with placental dysfunction. Genetic susceptibilities and poor placentation have been investigated intensively to understand the pathophysiology of PIH. It is currently thought that “poor placentation hypothesis”, in which extravillous trophoblasts fail to invade sufficiently the placental bed, explains in part maternal predisposition to this disease. Cumulative studies have suggested that hypoxic micromilieu of fetoplacental site, shear stress of uteroplacental blood flow, and aberrantly secreted proinflammatory substances into maternal circulation synergistically contribute to the progression of PIH. For example, soluble form of vascular endothelial growth factor receptor-1 (sVEGFR-1 and soluble form of CD105 are elevated in circulation of PIH mothers. However, it remains to be poorly understood the pathological events in the placenta during the last half of gestation as maternal systemic disorders get worse. For better understanding and effective therapeutic approaches to PIH, it is important to clarify pathological course of PIH-associated changes in the placenta. In this review, current understanding of placental development and the pathophysiology of PIH placenta are summarized. In

  5. MRI-based methods to detect placental and fetal brain abnormalities in utero.

    Girardi, Guillermina

    2016-04-01

    There are very few methods for screening women for pregnancy complications. Identification of pregnancies at risk would be of enormous clinical significance as would influence decisions made about pregnancy management and delivery. Adverse pregnancy outcomes such as obstetric antiphospholipid syndrome (APS) and preterm birth (PTB), characterized by placental insufficiency and abnormal fetal brain development, in mice and humans have been associated with activation of inflammatory pathways, in particular the complement cascade. Recently, antibodies against C3 activation products conjugated with contrast agent ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles were used to detect non-invasively sites of inflammation within the placenta and the fetal brain in mouse models of APS and PTB. In utero, magnetic resonance imaging (MRI)-based detection of C3 deposition in the placenta in the APS model was associated with signs of placental insufficiency and intrauterine growth restriction. In both models, fetal brain C3 deposition was associated with cortical axonal cytoarchitecture disruption and increased neurodegeneration. Proton magnetic resonance spectroscopy ((1)H MRS), another non invasive method, is used to identify metabolic abnormalities to predict fetal brain abnormalities. This review describes the recent development of preclinical MRI-based methods for the detection of inflammatory markers of placental insufficiency and abnormal fetal brain development and metabolism to predict pregnancy outcomes. PMID:26187242

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

    Nicholson Wanda K

    2008-09-01

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

  7. Animal Models to Study Placental Development and Function throughout Normal and Dysfunctional Human Pregnancy

    Grigsby, Peta L.

    2016-01-01

    Abnormalities of placental development and function are known to underlie many pathologies of pregnancy, including spontaneous preterm birth, fetal growth restriction and preeclampsia. A growing body of evidence also underscores the importance of placental dysfunction in the lifelong health of both mother and offspring. However, our knowledge regarding placental structure and function throughout pregnancy remains limited. Understanding the temporal growth and functionality of the human placen...

  8. Placental abnormalities in equine pregnancies generated by SCNT from one donor horse.

    Pozor, Malgorzata A; Sheppard, Barbara; Hinrichs, Katrin; Kelleman, Audrey A; Macpherson, Margo L; Runcan, Erin; Choi, Young-Ho; Diaw, Mouhamadou; Mathews, Philip M

    2016-10-01

    Placental changes associated with SCNT have been described in several species, but little information is available in this area in the horse. We evaluated the ultrasonographic, gross, and histopathological characteristics of placentas from three successful and five unsuccessful equine SCNT pregnancies, established using cells from a single donor horse. Starting at approximately 6-month gestation, the pregnancies were monitored periodically using transrectal (TR) and transabdominal (TA) ultrasonography (US) to examine the placentas, fetal fluids, and fetuses. Of the five mares that aborted, one mare did so suddenly without any abnormal signs detected by US and four had enlarged umbilical vessels visible on TA-US before abortion. Placental edema (TR-US) and intravascular thrombi in the umbilical cords were seen (TA-US) in two of these four mares; one mare aborted shortly after acute placental separation was identified on TA-US. In three mares that delivered live foals, TA-US showed engorged allantoic vessels and enlarged umbilical vessels. Two of these mares had placental thickening visible on TR-US, interpreted as a sign of placentitis, that subsided after aggressive medical treatment. Seven of the eight placentas were submitted for gross and histopathological examinations after delivery. All placentas had some degree of edema, abnormally engorged allantoic vessels, and enlarged umbilical vessels. Placentitis, large allantoic vesicles, cystic pouches in the fetal part of the cord, and hemorrhages and thrombi in the umbilical vessels were detected only in placentas from mares that aborted. Equine pregnancies resulting from SCNT may be associated with placental pathologies that can be detected using ultrasonography. However, interpreting their severity is difficult. Although placental abnormalities have been observed in SCNT pregnancies in other species, to the best of our knowledge, placentitis has not been previously reported and may be an important complication of

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

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

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

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

    2010-07-02

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

  11. Immunoinformatics of Placental Malaria Vaccine Development

    Jessen, Leon Eyrich

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

  12. Placental Development in Ongoing Pregnancy and Miscarriage

    A.D. Reus (Averil)

    2015-01-01

    markdownabstract__Abstract__ In this thesis three-dimensional ultrasound, three-dimensional power Doppler ultrasound, virtual reality and histologic examination of the chorionic villous vascularization were used to investigate early placental development in normal ongoing pregnancy as well as misca

  13. PPAR Signaling in Placental Development and Function

    Yaacov Barak

    2007-11-01

    Full Text Available With the major attention to the pivotal roles of PPARs in diverse aspects of energy metabolism, the essential functions of PPARγ and PPARβ/δ in placental development came as a surprise and were often considered a nuisance en route to their genetic analysis. However, these findings provided an opportune entrée into placental biology. Genetic and pharmacological studies, primarily of knockout animal models and cell culture, uncovered networks of PPARγ and PPARδ, their heterodimeric RXR partners, associated transcriptional coactivators, and target genes, that regulate various aspects of placental development and function. These studies furnish both specific information about trophoblasts and the placenta and potential hints about the functions of PPARs in other tissues and cell types. They reveal that the remarkable versatility of PPARs extends beyond the orchestration of metabolism to the regulation of cellular differentiation, tissue development, and trophoblast-specific functions. This information and its implications are the subject of this review.

  14. Association of coexisting morphological umbilical cord abnormality and clinical cord compromise with hypoxic and thrombotic placental histology.

    Stanek, Jerzy

    2016-06-01

    To assess the usefulness and limitations of placental histology when morphological umbilical cord (UC) abnormality coexists with clinical UC compromise, 5634 consecutive placentas were divided into four groups and statistically compared: group 1-182 placentas from pregnancies with clinical features of UC compromise (variable decelerations, UC entanglement, prolapse, or true knot at delivery); group 2-1355 placentas with abnormal UC morphology or insertion; group 3-152 placentas with at least one phenotype from group 1 and one from group 2; group 4-3945 placentas with no clinical or morphological UC-related phenotypes (control group).Differences were analyzed by ANOVA or χ (2). Of 68 phenotypes studied, 13 clinical and 18 placental phenotypes were statistically significant. In group 1, 2 phenotypes were most common (oligohydramnios and abnormal fetal heart rate tracing). In group 2, 6 phenotypes were most common, including 4 clinical (abnormal umbilical artery Dopplers, nonmacerated stillbirth, multiple pregnancy, and fetal growth restriction) and 2 placental. In group 3, 23 phenotypes were most common, including 7 clinical (gestational hypertension, polyhydramnios, induction of labor, cesarean section, macerated stillbirth, congenital malformations, and abnormal 3rd stage of labor) and 16 placental. The existence of clinical signs of UC compromise alone was associated with the absence of pathomorphological placental abnormalities. However, the coexistence of clinical and abnormal morphological UC phenotypes was statistically significantly associated with placental histological signs of decreased fetal blood flow, hypoxia (acute and chronic post uterine), shallow placental implantation, and/or amnion nodosum. Thus, confirmation of clinical UC compromise should not be expected on placental examination if no morphological UC abnormality or abnormal UC insertion has been found. PMID:26983702

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

    Fisher Susan J

    2004-07-01

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

  16. [Alcohol and pregnancy: diagnostic aspects and abnormalities in the placental vitamin A pathway].

    Sapin, V

    2008-01-01

    Maternal alcohol drinking during pregnancy is a reality in France leading to new-born specific clinical signs called "Fetal alcoholic syndrome/FAS" in 1.5 per 1000 births and to common clinical signs grouped into "Fetal Linked to Alcohol Spectrum Disorders" in 5 per 1000 births. Our works presented for the attribution of the SFBC 2007 price talked about two aspects of this public health problem. The first presented the recent evaluation of the alcohol consumption during pregnancy in Auvergne by the realization of the DATAMATER clinical and biological study on more than 800 "mother/baby" couples. We confirmed the reality of such maternal drinking (1.8 FAS per 1000 births) and also the useless of biological tools to help the diagnosis of the clinician where the clinical signs did not clearly belonged to FAS and when the maternal consumption was asked. The second aspect reviewed the placental abnormalities occurring during the FAS, which could explain the intra-uterine growth retardation. To better understand the genesis of such alterations, we proposed a new physio-pathological mechanism. The alcohol could alter the retinol (vitamin A) activation into retinoic acid, a fundamental morphogenic molecule for the optimal development and functions of the placenta. PMID:18957339

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

    Robert Klepacz

    2010-06-01

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

  18. Nodal regulates trophoblast differentiation and placental development.

    Ma, G T; Soloveva, V; Tzeng, S J; Lowe, L A; Pfendler, K C; Iannaccone, P M; Kuehn, M R; Linzer, D I

    2001-08-01

    Nodal has been thought to be an embryo-specific factor that regulates development, but nodal is also expressed in the mouse placenta beginning at midgestation, specifically in the spongiotrophoblasts. In an insertional null nodal mutant, not only is embryonic development disrupted, but mouse placental development is also grossly altered with the loss of the diploid spongiotrophoblasts and labyrinth and an expansion of the polyploid giant cell layer. A hypomorphic mutation in nodal results in an expansion of the giant cell and spongiotrophoblast layers, and a decrease in labyrinthine development. Expression of nodal in trophoblast cell cultures is sufficient to inhibit trophoblast giant cell differentiation, demonstrating that nodal can act directly on trophoblasts. The mechanism of nodal action includes the inhibition of junB gene transcription. These results suggest that nodal may be involved in redirecting trophoblast fate towards the midgestational expansion of the labyrinth region while maintaining the thin layer of trophoblast giant cells and the underlying layer of spongiotrophoblasts that form the boundary between the maternal and extraembryonic compartments. PMID:11456449

  19. The Value of Ultrasound and Magnetic Resonance Imaging in Diagnostics and Prediction of Morbidity in Cases of Placenta Previa with Abnormal Placentation

    The purpose of the study was to evaluate the role of ultrasound (US) and magnetic resonance imaging (MRI) in the diagnostics and management of abnormal placentation in women with placenta previa and to compare the morbidity associated with that to placenta previa alone. The study includes 100 pregnant women with placenta previa with and without abnormal placentation. The results of MRI and US in abnormal placentation were compared with post-operative data. The patients’ files were reviewed for assessment of operative and post-operative morbidity. The results of our statistical analysis were compared with data from the literature. US and MRI showed no significant difference in sensitivity and specificity in diagnosing abnormal placentation (97–100% and 94–100%, respectively). MRI was more sensitive than US for the detection of myometrial invasion and the type of abnormal placentation (73.5% and 47%, respectively). The difference between pre- and post-operative hemoglobin values and estimated blood loss were the most significant risk factors for abnormal placentation, added to risk factors known for placenta previa. Post-partum surgical complications and prolonged hospital stay were more common in the cases of placenta previa with abnormal placentation, however statistically insignificant. US and MRI are accurate imaging modalities for diagnosing abnormal placentation. MRI was more sensitive for the detection of the degree of placental invasion. The patient’s morbidity increased in cases with abnormal placentation. There was no significant difference in post operative-complications and hospitalization time due to pre-operative planning when the diagnosis was established with US and MRI

  20. Animal Models to Study Placental Development and Function throughout Normal and Dysfunctional Human Pregnancy.

    Grigsby, Peta L

    2016-01-01

    Abnormalities of placental development and function are known to underlie many pathologies of pregnancy, including spontaneous preterm birth, fetal growth restriction, and preeclampsia. A growing body of evidence also underscores the importance of placental dysfunction in the lifelong health of both mother and offspring. However, our knowledge regarding placental structure and function throughout pregnancy remains limited. Understanding the temporal growth and functionality of the human placenta throughout the entirety of gestation is important if we are to gain a better understanding of placental dysfunction. The utilization of new technologies and imaging techniques that could enable safe monitoring of placental growth and function in vivo has become a major focus area for the National Institutes of Child Health and Human Development, as evident by the establishment of the "Human Placenta Project." Many of the objectives of the Human Placenta Project will necessitate preclinical studies and testing in appropriately designed animal models that can be readily translated to the clinical setting. This review will describe the advantages and limitations of relevant animals such as the guinea pig, sheep, and nonhuman primate models that have been used to study the role of the placenta in fetal growth disorders, preeclampsia, or other maternal diseases during pregnancy. PMID:26752715

  1. MicroRNAs in Human Placental Development and Pregnancy Complications

    Chun Peng

    2013-03-01

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

  2. Sex-Specific Placental Responses in Fetal Development.

    Rosenfeld, Cheryl S

    2015-10-01

    The placenta is an ephemeral but critical organ for the survival of all eutherian mammals and marsupials. It is the primary messenger system between the mother and fetus, where communicational signals, nutrients, waste, gases, and extrinsic factors are exchanged. Although the placenta may buffer the fetus from various environmental insults, placental dysfunction might also contribute to detrimental developmental origins of adult health and disease effects. The placenta of one sex over the other might possess greater ability to respond and buffer against environmental insults. Given the potential role of the placenta in effecting the lifetime health of the offspring, it is not surprising that there has been a resurging interest in this organ, including the Human Placental Project launched by the National Institutes of Child Health and Human Development. In this review, we will compare embryological development of the laboratory mouse and human chorioallantoic placentae. Next, evidence that various species, including humans, exhibit normal sex-dependent structural and functional placental differences will be examined followed by how in utero environmental changes (nutritional state, stress, and exposure to environmental chemicals) might interact with fetal sex to affect this organ. Recent data also suggest that paternal state impacts placental function in a sex-dependent manner. The research to date linking placental maladaptive responses and later developmental origins of adult health and disease effects will be explored. Finally, we will focus on how sex chromosomes and epimutations may contribute to sex-dependent differences in placental function, the unanswered questions, and future directions that warrant further consideration. PMID:26241064

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

    Miguel A Garcia-Gonzalez

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

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

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

    2014-01-01

    The Amur tiger is a unique endangered species in the world, and thus, protection of its genetic resources is extremely important. In this study, an Amur tiger placenta cDNA library was constructed using the SMART cDNA Library Construction kit. A total of 508 colonies were sequenced, in which 205 (76%) genes were annotated and mapped to 74 KEGG pathways, including 29 metabolism, 29 genetic information processing, 4 environmental information processing, 7 cell motility, and 5 organismal system pathways. Additionally, PLAC8, PEG10 and IGF-II were identified after screening genes from the expressed sequence tags, and they were associated with placental development. These findings could lay the foundation for future functional genomic studies of the Amur tiger. PMID:25299101

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

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

    2014-01-01

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

  6. Development of Non-Viral, Trophoblast-Specific Gene Delivery for Placental Therapy

    Abd Ellah, Noura; Taylor, Leeanne; Troja, Weston; Owens, Kathryn; Ayres, Neil; Pauletti, Giovanni; Jones, Helen

    2015-01-01

    Low birth weight is associated with both short term problems and the fetal programming of adult onset diseases, including an increased risk of obesity, diabetes and cardiovascular disease. Placental insufficiency leading to intrauterine growth restriction (IUGR) contributes to the prevalence of diseases with developmental origins. Currently there are no therapies for IUGR or placental insufficiency. To address this and move towards development of an in utero therapy, we employ a nanostructure...

  7. Development of Non-Viral, Trophoblast-Specific Gene Delivery for Placental Therapy.

    Noura Abd Ellah

    Full Text Available Low birth weight is associated with both short term problems and the fetal programming of adult onset diseases, including an increased risk of obesity, diabetes and cardiovascular disease. Placental insufficiency leading to intrauterine growth restriction (IUGR contributes to the prevalence of diseases with developmental origins. Currently there are no therapies for IUGR or placental insufficiency. To address this and move towards development of an in utero therapy, we employ a nanostructure delivery system complexed with the IGF-1 gene to treat the placenta. IGF-1 is a growth factor critical to achieving appropriate placental and fetal growth. Delivery of genes to a model of human trophoblast and mouse placenta was achieved using a diblock copolymer (pHPMA-b-pDMAEMA complexed to hIGF-1 plasmid DNA under the control of trophoblast-specific promoters (Cyp19a or PLAC1. Transfection efficiency of pEGFP-C1-containing nanocarriers in BeWo cells and non-trophoblast cells was visually assessed via fluorescence microscopy. In vivo transfection and functionality was assessed by direct placental-injection into a mouse model of IUGR. Complexes formed using pHPMA-b-pDMAEMA and CYP19a-923 or PLAC1-modified plasmids induce trophoblast-selective transgene expression in vitro, and placental injection of PLAC1-hIGF-1 produces measurable RNA expression and alleviates IUGR in our mouse model, consequently representing innovative building blocks towards human placental gene therapies.

  8. Development of Non-Viral, Trophoblast-Specific Gene Delivery for Placental Therapy.

    Abd Ellah, Noura; Taylor, Leeanne; Troja, Weston; Owens, Kathryn; Ayres, Neil; Pauletti, Giovanni; Jones, Helen

    2015-01-01

    Low birth weight is associated with both short term problems and the fetal programming of adult onset diseases, including an increased risk of obesity, diabetes and cardiovascular disease. Placental insufficiency leading to intrauterine growth restriction (IUGR) contributes to the prevalence of diseases with developmental origins. Currently there are no therapies for IUGR or placental insufficiency. To address this and move towards development of an in utero therapy, we employ a nanostructure delivery system complexed with the IGF-1 gene to treat the placenta. IGF-1 is a growth factor critical to achieving appropriate placental and fetal growth. Delivery of genes to a model of human trophoblast and mouse placenta was achieved using a diblock copolymer (pHPMA-b-pDMAEMA) complexed to hIGF-1 plasmid DNA under the control of trophoblast-specific promoters (Cyp19a or PLAC1). Transfection efficiency of pEGFP-C1-containing nanocarriers in BeWo cells and non-trophoblast cells was visually assessed via fluorescence microscopy. In vivo transfection and functionality was assessed by direct placental-injection into a mouse model of IUGR. Complexes formed using pHPMA-b-pDMAEMA and CYP19a-923 or PLAC1-modified plasmids induce trophoblast-selective transgene expression in vitro, and placental injection of PLAC1-hIGF-1 produces measurable RNA expression and alleviates IUGR in our mouse model, consequently representing innovative building blocks towards human placental gene therapies. PMID:26473479

  9. Development and regulation of placental androstenedione during rat pregnancy

    The present study determined the ability of the rat placenta to convert [3H] pregnenolone (P5) substrate to [3H]Δ4A and [3H]T and to the intermediate steroid [3H]P4 in vitro on days 12 to 18 of gestation. Placental androgen formation increased and the amount of P4 formed and not further metabolized to Δ4A decreased during gestation, with the formation of Δ4A 2- to 4-fold greater (p3H]Δ4A to [3H]E2 was 2- to 4-fold greater (p3H]T. To determine if the ovary, specifically estrogen, regulates placental Δ4A production, rats were ovariectomized (OVX) on day 9 of gestation and given a Silastic capsule containing either E2 or vehicle. On day 14 OVX animals had an increased (p 4A and decreased (p 4. The formation of placental Δ4A invitro was correlated with elevated peripheral serum Δ4A concentrations in OVX animals, an effect which was reversed by E2

  10. Uterine and placental interactions during necrotic tip development in the pig from day 22 to 42 of gestation

    Placental development is important for fetal development and nutrient and waste transport. The pig, a litter bearing animal, has an epitheliochorial placenta that forms a noninvasive attachment with the uterine endometrium. Insufficient placental development is one of the primary causes of fetal dea...

  11. Artificial Neural Network for Transfer Function Placental Development: DCT and DWT Approach

    Mohammad Ayache

    2011-09-01

    Full Text Available The aim of our study is to propose an approach for transfer function placental development using ultrasound images. This approach is based to the selection of tissues, feature extraction by discrete cosine transform DCT, discrete wavelet transform DWT and classification of different grades of placenta by artificial neural network and especially the multi layer perceptron MLP. The proposed approach is tested for ultrasound images of placenta, resulting in 75% success rate of classification using DCT and 92% using DWT. The method based on multi resolution decomposition analysis and on supervised neural network technique MLP, seems a good method to study the transfer function of placental development in ultrasound.

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

    Han, V K; Carter, Anthony Michael

    2001-01-01

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

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

    Bianco-Miotto, Tina; Mayne, Benjamin T; Buckberry, Sam; Breen, James; Rodriguez Lopez, Carlos M; Roberts, Claire T

    2016-07-01

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

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

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

    2012-01-01

    The implantation of the blastocyst and early development of the placenta are crucial for the success of implantation and pregnancy. However, the formative stages of human placental development are largely unknown because of their existence in a 'black box' where access to samples is extremely lim...... mid-20th century and the renewed study of this period over the past 10 years as novel models of implantation have been developed....

  15. Embalse NGS: Abnormal event procedures development lifecycle

    Based on the present used philosophy in Canada and in Atucha Nuclear Generating Station (Argentina) it was decided to develop the Abnormal Event Procedures (EOP's) in a logical diagram format. The EOP's have in general two parts: the diagnosis and the operative action to mitigate the event. Some serious incidents can be resolved by the EOP's, but the philosophy is first, to satisfy the EOP's requirements. Taking into account the operating experience, the Final Safety Report and the results of simulations done by appropriate codes, it was possible to obtain the corresponding sequence for each abnormal event. With the information available in the Control Room (windows, alarms, trends, etc) for each part of the EOP's was associated the instrumentation that the operator must observe. 3 figs

  16. Artificial Neural Network for Transfer Function Placental Development: DCT and DWT Approach

    Mohammad Ayache; Mohamad Khalil; Francois Tranquart

    2011-01-01

    The aim of our study is to propose an approach for transfer function placental development using ultrasound images. This approach is based to the selection of tissues, feature extraction by discrete cosine transform DCT, discrete wavelet transform DWT and classification of different grades of placenta by artificial neural network and especially the multi layer perceptron MLP. The proposed approach is tested for ultrasound images of placenta, resulting in 75% success rate of classification usi...

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

    Ramazan Demir

    2011-07-01

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

  18. Expressional regulation of genes linked to immunity & programmed development in human early placental villi

    M A Khan

    2014-01-01

    Full Text Available Background & objectives: During 6 to 8 wk of gestation, human placental villi show a complex pattern of morphogenesis. There is however, no large scale gene expression study exploring the temporal pattern of the developmental molecular networks in placental villi during the early weeks of gestation. We evaluated the transcriptome profiling of humn placental villus samples obtained from fertile women with voluntarily terminated normal pregnancies between 6-8 wk of gestation. Methods: Transcriptomic profiles of individual human placental villous samples from 25 women with normal pregnancies during 6 to 8 wk of gestation were examined using human whole genome expression arrays. Quantitative RT-PCR validation of copy numbers of transcripts for selected 15 genes and exploratory analysis of the microarray data revealed a high degree of quality assurance supportive of further clustering and differential analyses. Immunoblot and immunohistochemical analysis of selected five candidate proteins (CAGE1, CD9, SLC6A2, TANK and VEGFC based on transcript profiles were done to assess the pattern of down stream informational flow. Results: A large number (~9K of genes with known functions were expressed in the experimental samples. The clustering analysis identified three major expression clusters with gestational age, and four co-expressional clusters. Differential analysis identified a highly discrete regulatory process involving only about 160 genes. Immunochemical analysis of selected candidate proteins based on transcript profiles revealed generally synchronous expression in human early placental villi. Interpretation & conclusions: Several signaling pathways linked to immunity (COL1, JAK2, JAK3, IL12, IL13, IL15, IL27, STAT3 and STAT5 were downregulated, while genes of the enriched category of antiviral immunity (ATF/AP1, IL10R and OAS were clearly over-expressed. Transcriptional integration supportive of programmed development was observed in first

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

    Padma Murthi

    2011-01-01

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

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

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

    2011-01-01

    In addition to its role in the prevention of neural tube defects, folic acid has many other physiological functions, including cell proliferation, DNA replication, and antioxidant protection. The aim of this study was to determine the role that folic acid has in regulating placental trophoblast development. Placental explants from placentae at gestational age 7 wk (n ¼ 3) were cultured in folic acid at concentrations of 106 M, 108 M, and 1010 M. Extravillous trophoblast (EVT) invasion was ass...

  1. The peroxisome proliferator-activated receptors under epigenetic control in placental metabolism and fetal development.

    Lendvai, Ágnes; Deutsch, Manuel J; Plösch, Torsten; Ensenauer, Regina

    2016-05-15

    The placental metabolism can adapt to the environment throughout pregnancy to both the demands of the fetus and the signals from the mother. Such adaption processes include epigenetic mechanisms, which alter gene expression and may influence the offspring's health. These mechanisms are linked to the diversity of prenatal environmental exposures, including maternal under- or overnutrition or gestational diabetes. The peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that contribute to the developmental plasticity of the placenta by regulating lipid and glucose metabolism pathways, including lipogenesis, steroidogenesis, glucose transporters, and placental signaling pathways, thus representing a link between energy metabolism and reproduction. Among the PPAR isoforms, PPARγ appears to be the main modulator of mammalian placentation. Certain fatty acids and lipid-derived moieties are the natural activating PPAR ligands. By controlling the amounts of maternal nutrients that go across to the fetus, the PPARs play an important regulatory role in placenta metabolism, thereby adapting to the maternal nutritional status. As demonstrated in animal studies, maternal nutrition during gestation can exert long-term influences on the PPAR methylation pattern in offspring organs. This review underlines the current state of knowledge on the relationship between environmental factors and the epigenetic regulation of the PPARs in placenta metabolism and offspring development. PMID:26860983

  2. Computational placental pathology: using placental geometry to assess placental function

    Li, Jenny (Jiazhen)

    2009-01-01

    Placental pathologists diagnose disease based on examining the placenta. It is hypothesized that poor blood vessel coverage may be detrimental to fetal development and may lead to low birth weight. In this project, geometrical measures of the placental structure are computed based on the total area of vessels and the vessel coverage on an important part of the placenta known as the chorionic plate. Vessel coverage is measured by the average of the distance from every point on the chorionic pl...

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

    Juanmahel Davila

    2015-08-01

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

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

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

    2015-08-01

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

  5. Mast Cells and Histamine: Do They Influence Placental Vascular Network and Development in Preeclampsia?

    Grzegorz Szewczyk

    2012-01-01

    Full Text Available The physiological course of pregnancy is closely related to adequate development of the placenta. Shallow invasion of trophoblast as well as decreased development of the placental vascular network are both common features of preeclampsia. To better understand the proangiogenic features of mast cells, in this study we aim to identify the potential relationship between the distribution of mast cells within the placenta and vascular network development. Material and Methods. Placentas from preeclampsia-complicated pregnancies (=11 and from physiological pregnancies (=11 were acquired after cesarean section. The concentration of histamine was measured, and immunohistochemical staining for mast cell tryptase was performed. Morphometric analysis was then performed. Results. We noticed significant differences between the examined groups. Notably, in the preeclampsia group compared to the control group, we observed a higher mean histamine concentration, higher mast cell density (MCD, lower mean mast cell (MMCA and lower vascular/extravascular (V/EVT index. In physiological pregnancies, a positive correlation was observed between the histamine concentration and V/VEVT index as well as MCD and the V/VEVT index. In contrast, a negative correlation was observed between MMCA and the V/EVT index in physiological pregnancies. Conclusions. Based on the data from our study, we suggest that a differential distribution of mast cells and corresponding changes in the concentration of histamine are involved in the defective placental vascularization seen in preeclamptic placentas.

  6. Effect of empty uterine space on birth intervals and fetal and placental development in pigs.

    Vallet, J L; Freking, B A; Miles, J R

    2011-05-01

    A substantial loss of embryos occurs between Days 30 and 40 of pregnancy in the pig under crowded intrauterine conditions, but it is not clear whether this loss affects the growth of adjacent conceptuses. Birth intervals are known to increase with decreasing litter size, but the factors responsible are unknown. Two possibilities are that increased birth weight associated with reduced litter size and the empty uterine space and resulting constricted uterine regions that occur in pigs with small litters may impair piglet delivery. To address these, pregnant gilts were laparotomized on Day 35 of pregnancy and one or two fetuses were manually crushed through the uterine wall on the ovarian or cervical end of each uterine horn to create an empty uterine space behind or in front of the litter of piglets, respectively, in relation to the route of delivery from the uterus. A subset of gilts was slaughtered at 105 days of gestation to confirm that the empty uterine spaces were successfully created and to determine their effects on placental and fetal weights of adjacent conceptuses. At slaughter, the lengths of all externally visible empty constricted regions of the uterus were measured. The uterine horns were opened and the lengths of each placenta were measured from the umbilicus toward the ovary and toward the cervix to assess whether placentas developed symmetrically, and then each fetus and placenta was weighed. Fetal crushing successfully created constricted empty uterine regions on the ovarian and cervical ends of the uterine horns. Ovarian-side placental lengths were greater than cervical-side for conceptuses adjacent to fetuses crushed on the ovarian end of the horn. Cervical-side placental lengths were greater than ovarian-side for conceptuses adjacent to fetuses crushed on the cervical end. Both placental and fetal weights were greater (10% and 6%, respectively, Pcrushed fetuses compared to nonadjacent conceptuses. Remaining gilts were farrowed to determine the

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

    ZHU Ying; WU Chaoying; SUN Yongyu

    2007-01-01

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

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

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

    2015-10-30

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

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

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

    2016-09-01

    The placenta is an essential organ formed during pregnancy that mainly transfers nutrients from the mother to the fetus. Nutrients taken up by the placenta are required for its own growth and development and to optimize fetal growth. Hence, placental function is an important determinant of pregnancy outcome. Among various nutrients, fatty acids, especially long-chain polyunsaturated fatty acids (LCPUFAs), including omega 3 and omega 6 fatty acids, are essential for placental development from the time of implantation. Studies have associated these LCPUFAs with placental development through their roles in regulating oxidative stress, angiogenesis, and inflammation, which may in turn influence their transfer to the fetus. The placenta has a heterogeneous morphology with variable regional vasculature, oxidative stress, and LCPUFA levels in healthy pregnancies depending upon the location within the placenta. However, these regional structural and functional parameters are found to be disturbed in pathological conditions, such as preeclampsia (PE), thereby affecting pregnancy outcome. Hence, the alterations in LCPUFA metabolism and transport in different regions of the PE placenta as compared with normal placenta could potentially be contributing to the pathological features of PE. The regional variations in development and function of the placenta and its possible association with placental LCPUFA metabolism and transport in normal and PE pregnancies are discussed in this review. WIREs Dev Biol 2016, 5:582-597. doi: 10.1002/wdev.238 For further resources related to this article, please visit the WIREs website. PMID:27239793

  10. Mechanisms of abnormal brain development leading to transsexualism (review

    L. F. Kurilo

    2014-11-01

    Full Text Available Overview of national and world literature on sexual autoidentification is analyzed. Prenatal brain development abnormalities leading to transsexualism are discussed. Results of own cytogenetic analysis, ооgenesis and spermatоgenesis examination are reported.

  11. Mechanisms of abnormal brain development leading to transsexualism (review)

    L. F. Kurilo; S. Sh. Khayat; S. Yu. Kalinchenko; B. Yu. Slonimskiy; T. M. Sorokina

    2014-01-01

    Overview of national and world literature on sexual autoidentification is analyzed. Prenatal brain development abnormalities leading to transsexualism are discussed. Results of own cytogenetic analysis, ооgenesis and spermatоgenesis examination are reported.

  12. Imaging and assessment of placental function.

    Moran, Mary

    2011-09-01

    The placenta is the vital support organ for the developing fetus. This article reviews current ultrasound (US) methods of assessing placental function. The ability of ultrasound to detect placental pathology is discussed. Doppler technology to investigate the fetal, placental, and maternal circulations in both high-risk and uncomplicated pregnancies is discussed and the current literature on the value of three-dimensional power Doppler studies to assess placental volume and vascularization is also evaluated. The article highlights the need for further research into three-dimensional ultrasound and alternative methods of placental evaluation if progress is to be made in optimizing placental function assessment.

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

    Y.K. Sinzato

    2011-03-01

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

  14. Abnormal coronary tree development in embryonic hypoxia

    Naňka, O.; Fikrle, P.; Křížová, D.; Sedmera, David; Grim, M.

    Bratislava : Slovenská anatomická společnost, 2007, s. 78-78. [Sjezd Slovenské anatomické společnosti s mezinárodní účastí /43./ a sjezd Slovenské histochemické společnosti s mezinárodní účastí /42./. Bratislava (SK), 09.09.2007-12.09.2007] Institutional research plan: CEZ:AV0Z50450515 Keywords : coronary tree development Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  15. [The growing spine : Normal and abnormal development].

    Stücker, R

    2016-06-01

    Growth of the pediatric spine occurs in phases. The first 5 years of life are characterized by rapid growth. The lower extremities and trunk contribute equally to the entire growth by 50 % each. In the following years, until the onset of puberty, a steady but reduced rate of growth is observed. During these years a T1-S1 growth of only 1 cm per year can be detected and the spine contributes only one third to the entire growth. Puberty consists of an acceleration phase lasting 2 years. In the first year of this phase the growth peak of the extremities and in the following year the growth peak of the spine can be noticed. The ensuing deceleration phase of puberty lasts for 3 years. During that period the development of the Risser sign, menarche, and fusion of the trochanter epiphysis are taking place. Clinical parameters such as sitting height, standing height, and arm span may be used to evaluate growth. Important radiological parameters include the Risser sign, the determination of skeletal age according to Greulich and Pyle, and the T1-T12 height. The use of the olecranon method during the ascending phase of puberty can be recommended. Problems of the developing spine may include malformations, developmental disruptions or deformations. According to their manifestations they have a different prognosis, which can be estimated by knowledge of residual growth and the typical course of spinal growth in childhood. PMID:27250620

  16. Interleukin-11 alters placentation and causes preeclampsia features in mice.

    Winship, Amy L; Koga, Kaori; Menkhorst, Ellen; Van Sinderen, Michelle; Rainczuk, Katarzyna; Nagai, Miwako; Cuman, Carly; Yap, Joanne; Zhang, Jian-Guo; Simmons, David; Young, Morag J; Dimitriadis, Evdokia

    2015-12-29

    Preeclampsia (PE) is a pregnancy-specific disorder characterized by hypertension and proteinuria after 20 wk gestation. Abnormal extravillous trophoblast (EVT) invasion and remodeling of uterine spiral arterioles is thought to contribute to PE development. Interleukin-11 (IL11) impedes human EVT invasion in vitro and is elevated in PE decidua in women. We demonstrate that IL11 administered to mice causes development of PE features. Immunohistochemistry shows IL11 compromises trophoblast invasion, spiral artery remodeling, and placentation, leading to increased systolic blood pressure (SBP), proteinuria, and intrauterine growth restriction, although nonpregnant mice were unaffected. Real-time PCR array analysis identified pregnancy-associated plasma protein A2 (PAPPA2), associated with PE in women, as an IL11 regulated target. IL11 increased PAPPA2 serum and placental tissue levels in mice. In vitro, IL11 compromised primary human EVT invasion, whereas siRNA knockdown of PAPPA2 alleviated the effect. Genes regulating uterine natural killer (uNK) recruitment and differentiation were down-regulated and uNK cells were reduced after IL11 treatment in mice. IL11 withdrawal in mice at onset of PE features reduced SBP and proteinuria to control levels and alleviated placental labyrinth defects. In women, placental IL11 immunostaining levels increased in PE pregnancies and in serum collected from women before development of early-onset PE, shown by ELISA. These results indicate that elevated IL11 levels result in physiological changes at the maternal-fetal interface, contribute to abnormal placentation, and lead to the development of PE. Targeting placental IL11 may provide a new treatment option for PE. PMID:26655736

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

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

    2009-01-01

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

  18. Comprehensive Imaging Review of Abnormalities of the Placenta.

    Zaidi, Sadaf F; Moshiri, Mariam; Osman, Sherif; Robinson, Tracy J; Siebert, Joseph R; Bhargava, Puneet; Katz, Douglas S

    2016-03-01

    The placenta has a fundamental role in fetal health and functions as an important bridge to normal fetal development throughout pregnancy. A complete fetal ultrasound (US) survey should include full assessment of the placenta for any possible abnormalities. Placental diseases range from abnormal morphology, size, location, extent, and degree of placentation, to abruption and the presence of rare placental neoplasms of benign or malignant nature. Some of these conditions are associated with other diseases including aneuploidies, and their discovery should alert the radiologist to perform a very thorough fetal US examination. At times, a fetal karyotype may be needed to provide additional information. Timely detection of placental abnormalities can alert the clinician regarding the need to make important management decisions to reduce fetal and maternal morbidity and mortality. Familiarity with the normal and abnormal imaging appearance of the placenta is therefore necessary for the radiologist. Ultrasound with Doppler is the initial imaging modality of choice for placental assessment. Magnetic resonance imaging serves as a problem-solving examination in instances where the US findings are equivocal or where additional information is needed. Computed tomography has a limited role in the evaluation of placental disease because of its relatively limited tissue characterization and in particular because of the resultant direct radiation exposure of the fetus. However, in specific instances, particularly after trauma, computed tomography can provide invaluable information for patient management. PMID:26938032

  19. Characterization of placental cholesterol transport

    Lindegaard, Marie L; Wassif, Christopher A; Vaisman, Boris;

    2008-01-01

    cholesterol, in utero treatment with TO901317 resulted in increased cholesterol content in Dhcr7(-/-) embryos. Our data support the hypothesis that Abca1, and possibly Sr-b1, contributes to transport maternal cholesterol to the developing fetus. Furthermore, we show, as a proof of principle, that modulating......Patients with Smith-Lemli-Opitz syndrome (SLOS) are born with multiple congenital abnormalities. Postnatal cholesterol supplementation is provided; however, it cannot correct developmental malformations due to in utero cholesterol deficit. Increased transport of cholesterol from maternal to fetal...... embryonic days 13.5 and 18.5 in placental tissue; whereas, Sr-b1 expression decreased. To examine the functional role of Abca1, Abcg1 and Sr-b1 we measured the maternal-fetal transfer of (14)C-cholesterol in corresponding mutant embryos. Disruption of either Abca1 or Sr-b1 decreased cholesterol transfer by...

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

    Aghababaei, Mahroo; Beristain, Alexander G

    2015-04-01

    Placental development is a highly regulated process requiring signals from both fetal and maternal uterine compartments. Within this complex system, trophoblasts, placental cells of epithelial lineage, form the maternal-fetal interface controlling nutrient, gas and waste exchange. The commitment of progenitor villous cytotrophoblasts to differentiate into diverse trophoblast subsets is a fundamental process in placental development. Differentiation of trophoblasts into invasive stromal- and vascular-remodeling subtypes is essential for uterine arterial remodeling and placental function. Inadequate placentation, characterized by defects in trophoblast differentiation, may underlie the earliest cellular events driving pregnancy disorders such as preeclampsia and fetal growth restriction. Molecularly, invasive trophoblasts acquire characteristics defined by profound alterations in cell-cell and cell-matrix adhesion, cytoskeletal reorganization and production of proteolytic factors. To date, most studies have investigated the importance of the matrix metalloproteinases (MMPs) and their ability to efficiently remodel components of the extracellular matrix (ECM). However, it is now becoming clear that besides MMPs, other related proteases regulate trophoblast invasion via mechanisms other than ECM turnover. In this review, we will summarize the current knowledge on the regulation of trophoblast invasion by members of the metzincin family of metalloproteinases. Specifically, we will discuss the emerging roles that A Disintegrin and Metalloproteinases (ADAMs) play in placental development, with a particular focus on the ADAM subtype, ADAM12. PMID:25589360

  1. Regulation of cell surface protease matriptase by HAI2 is essential for placental development, neural tube closure and embryonic survival in mice

    Szabo, Roman; Hobson, John P.; Christoph, Kristina; Kosa, Peter; List, Karin; Bugge, Thomas H.

    2009-01-01

    Hypomorphic mutations in the human SPINT2 gene cause a broad spectrum of abnormalities in organogenesis, including organ and digit duplications, atresia, fistulas, hypertelorism, cleft palate and hamartoma. SPINT2 encodes the transmembrane serine protease inhibitor HAI2 (placental bikunin), and the severe developmental effects of decreased HAI2 activity can be hypothesized to be a consequence of excess pericellular proteolytic activity. Indeed, we show here that HAI2 i...

  2. Skeletal development in the African elephant and ossification timing in placental mammals

    Hautier, Lionel; Stansfield, Fiona J.; Allen, W. R. Twink; Asher, Robert J

    2012-01-01

    We provide here unique data on elephant skeletal ontogeny. We focus on the sequence of cranial and post-cranial ossification events during growth in the African elephant (Loxodonta africana). Previous analyses on ossification sequences in mammals have focused on monotremes, marsupials, boreoeutherian and xenarthran placentals. Here, we add data on ossification sequences in an afrotherian. We use two different methods to quantify sequence heterochrony: the sequence method and event-paring/Pars...

  3. Influence of endurance exercise and diet on human placental development and fetal growth.

    Clapp, J F

    2006-01-01

    The delivery of oxygen and substrate to the maternal-fetal interphase is the major maternal environmental stimulus which either up- or down-regulates feto-placental growth. During pregnancy, sustained exercise sessions cause an intermittent reduction in oxygen and substrate delivery to the interphase that may exceed 50% during the exercise but, it is probable that regular bouts of sustained exercise or exercise training may improve oxygen and substrate delivery at rest. The type of maternal carbohydrate intake (low- versus high-glycemic sources) and food intake frequency also influence substrate availability through their effects on maternal blood glucose levels and insulin sensitivity. As a result, different exercise regimens and/or different types of carbohydrate intake modify feto-placental growth. The magnitude and direction of the effect is determined by their average 24-h effect on oxygen and substrate availability at different time-points in pregnancy. In general, exercise in early and mid pregnancy stimulates placental growth while the relative amount of exercise in late pregnancy determines its effect on late fetal growth. Low-glycemic food sources in the diet decrease growth rate and size at birth while high-glycemic food sources increase it. Thus, it may be possible to improve pregnancy outcomes in both healthy, low-risk women and a variety of high-risk populaces by simply modifying maternal physical activity and dietary carbohydrate intake during pregnancy. PMID:16165206

  4. Assessment of placental transfer and the effect on embryo-fetal development of a humanized monoclonal antibody targeting lymphotoxin-alpha in non-human primates.

    Wang, Hong; Schuetz, Chris; Arima, Akihiro; Chihaya, Yutaka; Weinbauer, Gerhard F; Habermann, Gunnar; Xiao, Jim; Woods, Cynthia; Grogan, Jane; Gelzleichter, Thomas; Cain, Gary

    2016-08-01

    An enhanced embryo-fetal development study was conducted in cynomolgus monkeys using pateclizumab, a humanized IgG1 monoclonal antibody (mAb) targeting lymphotoxin-alpha. Pateclizumab administration between gestation days (GD) 20 and 132 did not induce maternal or developmental toxicities. The ratio of fetal-to-maternal serum concentration of pateclizumab was 0.73% on GD 50 and 61% by GD 139. Decreased fetal inguinal lymph node-to-body weight ratio was present in the high-dose group without microscopic abnormalities, a change attributable to inhibition of lymphocyte recruitment, which is a pharmacologic effect of pateclizumab during late lymph node development. The effect was observed in inguinal but not submandibular or mesenteric lymph nodes; this was attributed to differential susceptibility related to sequential lymph node development. Placental transfer of therapeutic IgG1 antibodies; thus, begins during the first trimester in non-human primates. Depending on the potency and dose levels administered, antibody levels in the fetus may be pharmacologically or toxicologically relevant. PMID:27211603

  5. Consequences of gestational and pregestational diabetes on placental function and birth weight

    2011-01-01

    Maternal diabetes constitutes an unfavorable environment for embryonic and fetoplacental development. Despite current treatments, pregnant women with pregestational diabetes are at increased risk for congenital malformations, materno-fetal complications, placental abnormalities and intrauterine malprogramming. The complications during pregnancy concern the mother (gravidic hypertension and/or preeclampsia, cesarean section) and the fetus (macrosomia or intrauterine growth restriction, shoulde...

  6. Sonographic spectrum of placental abruption.

    Nyberg, D A; Cyr, D R; Mack, L A; Wilson, D A; Shuman, W P

    1987-01-01

    Fifty-seven cases of placental abruption detected by sonography were retrospectively reviewed. The location of hemorrhage was subchorionic in 46 cases (81%), retroplacental in nine cases (16%), and preplacental in two cases (4%). Subchorionic hematomas were more frequently shown in the 33 patients presenting before 20 menstrual weeks (91%) than in the 24 patients presenting after 20 weeks (67%). The echogenicity of hemorrhage depended on the time the sonogram was performed relative to the onset of symptoms: Acute hemorrhage was hyperechoic to isoechoic compared with the placenta, while resolving hematomas became hypoechoic within 1 week and sonolucent within 2 weeks. Acute hemorrhage was occasionally difficult to distinguish from the adjacent placenta. This occurred in five retroplacental hematomas that showed only an abnormally thick and heterogeneous placenta. Nine cases of placental abruption were initially confused with other mass lesions. Placental abruption causes a wide spectrum of sonographic findings that may be overlooked or misdiagnosed. PMID:3538831

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

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

    2016-01-01

    BAHD1 is a vertebrate protein that promotes heterochromatin formation and gene repression in association with several epigenetic regulators. However, its physiological roles remain unknown. Here, we demonstrate that ablation of the Bahd1 gene results in hypocholesterolemia, hypoglycemia and decreased body fat in mice. It also causes placental growth restriction with a drop of trophoblast glycogen cells, a reduction of fetal weight and a high neonatal mortality rate. By intersecting transcriptome data from murine Bahd1 knockout (KO) placentas at stages E16.5 and E18.5 of gestation, Bahd1-KO embryonic fibroblasts, and human cells stably expressing BAHD1, we also show that changes in BAHD1 levels alter expression of steroid/lipid metabolism genes. Biochemical analysis of the BAHD1-associated multiprotein complex identifies MIER proteins as novel partners of BAHD1 and suggests that BAHD1-MIER interaction forms a hub for histone deacetylases and methyltransferases, chromatin readers and transcription factors. We further show that overexpression of BAHD1 leads to an increase of MIER1 enrichment on the inactive X chromosome (Xi). In addition, BAHD1 and MIER1/3 repress expression of the steroid hormone receptor genes ESR1 and PGR, both playing important roles in placental development and energy metabolism. Moreover, modulation of BAHD1 expression in HEK293 cells triggers epigenetic changes at the ESR1 locus. Together, these results identify BAHD1 as a core component of a chromatin-repressive complex regulating placental morphogenesis and body fat storage and suggest that its dysfunction may contribute to several human diseases. PMID:26938916

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

    Bergamaschi Antonio

    2008-09-01

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

  9. Emotion processes in normal and abnormal development and preventive intervention.

    Izard, Carroll E; Fine, Sarah; Mostow, Allison; Trentacosta, Christopher; Campbell, Jan

    2002-01-01

    We present an analysis of the role of emotions in normal and abnormal development and preventive intervention. The conceptual framework stems from three tenets of differential emotions theory (DET). These principles concern the constructs of emotion utilization; intersystem connections among modular emotion systems, cognition, and action; and the organizational and motivational functions of discrete emotions. Particular emotions and patterns of emotions function differentially in different periods of development and in influencing the cognition and behavior associated with different forms of psychopathology. Established prevention programs have not emphasized the concept of emotion as motivation. It is even more critical that they have generally neglected the idea of modulating emotions, not simply to achieve self-regulation, but also to utilize their inherently adaptive functions as a means of facilitating the development of social competence and preventing psychopathology. The paper includes a brief description of a theory-based prevention program and suggestions for complementary targeted interventions to address specific externalizing and internalizing problems. In the final section, we describe ways in which emotion-centered preventions can provide excellent opportunities for research on the development of normal and abnormal behavior. PMID:12549703

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

    Elliot, Michael G; Crespi, Bernard J

    2015-03-01

    The relationship between phenotypic variation arising through individual development and phenotypic variation arising through diversification of species has long been a central question in evolutionary biology. Among humans, reduced placental invasion into endometrial tissues is associated with diseases of pregnancy, especially pre-eclampsia, and reduced placental invasiveness has also evolved, convergently, in at least 10 lineages of eutherian mammals. We tested the hypothesis that a common genetic basis underlies both reduced placental invasion arising through a developmental process in human placental disease and reduced placental invasion found as a derived trait in the diversification of Euarchontoglires (rodents, lagomorphs, tree shrews, colugos and primates). Based on whole-genome analyses across 18 taxa, we identified 1254 genes as having evolved adaptively across all three lineages exhibiting independent evolutionary transitions towards reduced placental invasion. These genes showed strong evidence of enrichment for associations with pre-eclampsia, based on genetic-association studies, gene-expression analyses and gene ontology. We further used in silico prediction to identify a subset of 199 genes that are likely targets of natural selection during transitions in placental invasiveness and which are predicted to also underlie human placental disorders. Our results indicate that abnormal ontogenies can recapitulate major phylogenetic shifts in mammalian evolution, identify new candidate genes for involvement in pre-eclampsia, imply that study of species with less-invasive placentation will provide useful insights into the regulation of placental invasion and pre-eclampsia, and recommend a novel comparative functional-evolutionary approach to the study of genetically based human disease and mammalian diversification. PMID:25602073

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

    Sunn Nana

    2006-02-01

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

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

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

    2010-04-15

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

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

    陈镇燕; 李静; 黄光英

    2012-01-01

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

  14. Foetal and placental growth in the mouse after pre-implantation development in vitro under oxygen concentrations of 5 and 20%.

    Harlow, G M; Quinn, P

    1979-06-01

    Blastocysts which developed from two-cell mouse embryos in culture tubes containing an atmosphere with 20% oxygen had approximately 20% fewer blastomeres than blastocysts which developed under an oxygen concentration of 5%. When these smaller blastocysts were transferred to the uteri of pseudopregnant foster mothers, the foetuses developing were as viable as those developing from blastocysts cultured under 5% oxygen, indicating their ability to regulate for a lower blastomere number by at least day 17 of development. The transfer operation itself had no adverse effect on foetal or placental growth. However, culture of blastocysts in vitro did depress foetal though not placental growth, suggesting that the inner cell mass is more susceptible than the trophectoderm to culture in vitro. Foetal but not placental growth was lower following the transfer of blastocysts to a day-3 rather than a day-4 uterus. Four cases of placental fusion were found. In one case, the foetuses were contained within the same embryonic sac and may have been twins. PMID:508209

  15. Pregnancy Complications: Placental Abruption

    ... belly is harmed from a car accident or physical abuse . If you've had a placental abruption before, ... belly is harmed from a car accident or physical abuse . If you've had a placental abruption before, ...

  16. Slc20a2 deficiency results in fetal growth restriction and placental calcification associated with thickened basement membranes and novel CD13 and lamininα1 expressing cells.

    Wallingford, Mary C; Gammill, Hilary S; Giachelli, Cecilia M

    2016-03-01

    The essential nutrient phosphorus must be taken up by the mammalian embryo during gestation. The mechanism(s) and key proteins responsible for maternal to fetal phosphate transport have not been identified. Established parameters for placental phosphate transport match those of the type III phosphate transporters, Slc20a1 and Slc20a2. Both members are expressed in human placenta, and their altered expression is linked to preeclampsia. In this study, we tested the hypothesis that Slc20a2 is required for placental function. Indeed, complete deficiency of Slc20a2 in either the maternal or embryonic placental compartment results in fetal growth restriction. We found that Slc20a2 null mice can reproduce, but are subviable; ∼50% are lost prior to weaning age. We also observed that 23% of Slc20a2 deficient females develop pregnancy complications at full term, with tremors and placental abnormalities including abnormal vascular structure, increased basement membrane deposition, abundant calcification, and accumulation of novel CD13 and lamininα1 positive cells. Together these data support that Slc20a2 deficiency impacts both maternal and neonatal health, and Slc20a2 is required for normal placental function. In humans, decreased levels of placental Slc20a1 and Slc20a2 have been correlated with early onset preeclampsia, a disorder that can manifest from placental dysfunction. In addition, preterm placental calcification has been associated with poor pregnancy outcomes. We surveyed placental calcification in human preeclamptic placenta samples, and detected basement membrane-associated placental calcification as well as a comparable lamininα1 positive cell type, indicating that similar mechanisms may underlie both human and mouse placental calcification. PMID:26952749

  17. [THE CHARACTER OF EXPRESSION AND THE ROLE OF APOPTOSIS MARKERS IN THE DEVELOPMENT OF PLACENTAL DYSFUNCTION IN PREGNANT WITH UROGENITAL INFECTIONS].

    Shcherbuna, N; Vygovskaya, L; Kapustnik, N

    2016-02-01

    The aim of the current study was to examine the expression level and possibilities of apoptotic markers in realization of placental insufficiency in pregnant women with urogenital infections. The study was conducted on 250 pregnant women with urogenital infections (1-st group - 50 pregnant women with bacterial infections (Chlamydia, ureaplasma, mycoplasma), 2-nd group - 50 pregnant women with viral infections (CMV and herpes simplex virus), 3-rd group - 150 patients with mixed viral and bacterial infections) and 50 pregnant women with normal pregnancy. The content of apoptosis inducers: sFasL and TNF-α in blood serum of pregnant women was determined; the level of caspase-3 in placental sample was analyzed; sonographic examination of the placenta was performed. Maximal indices of apoptosis inducers were observed in the 3-rd group (with mixed viral and bacterial infections). Changes in the placenta according to ultrasound data were determined in all pregnant women with urogenital infections. It was suggested that increased placental cell death in apoptosis might be one of the key points, triggering the development of placental dysfunction. PMID:27001779

  18. Intrapritoneal Hemorrhage after Placental Abruption

    Nahid Sakhavar

    2012-06-01

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

  19. Mouse placental macrophages have a decreased ability to present antigen.

    Chang, M D; Pollard, J W; Khalili, H; Goyert, S M; Diamond, B.

    1993-01-01

    Large numbers of macrophages can be found in an animal's uteroplacental unit. This high concentration of macrophages suggests they must play an important role during placental development. To gain a better understanding of the functional capacity of placental macrophages, we have obtained a highly enriched placental macrophage culture and have derived several cell lines from this population. Both placental macrophages and cell lines show colony-stimulating factor 1-dependent growth, express F...

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

    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

  1. Placental Evolution within the Supraordinal Clades of Eutheria with the Perspective of Alternative Animal Models for Human Placentation

    Andrea Mess

    2014-01-01

    Here a survey of placental evolution is conducted. Placentation is a key factor for the evolution of placental mammals that had evolved an astonishing diversity. As a temporary organ that does not allow easy access, it is still not well understood. The lack of data also is a restriction for better understanding of placental development, structure, and function in the human. Animal models are essential, because experimental access to the human placenta is naturally restricted. However, there i...

  2. Placental origins of adverse pregnancy outcomes: potential molecular targets: an Executive Workshop Summary of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

    Ilekis, John V; Tsilou, Ekaterini; Fisher, Susan; Abrahams, Vikki M; Soares, Michael J; Cross, James C; Zamudio, Stacy; Illsley, Nicholas P; Myatt, Leslie; Colvis, Christine; Costantine, Maged M; Haas, David M; Sadovsky, Yoel; Weiner, Carl; Rytting, Erik; Bidwell, Gene

    2016-07-01

    Although much progress is being made in understanding the molecular pathways in the placenta that are involved in the pathophysiology of pregnancy-related disorders, a significant gap exists in the utilization of this information for the development of new drug therapies to improve pregnancy outcome. On March 5-6, 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health sponsored a 2-day workshop titled Placental Origins of Adverse Pregnancy Outcomes: Potential Molecular Targets to begin to address this gap. Particular emphasis was given to the identification of important molecular pathways that could serve as drug targets and the advantages and disadvantages of targeting these particular pathways. This article is a summary of the proceedings of that workshop. A broad number of topics were covered that ranged from basic placental biology to clinical trials. This included research in the basic biology of placentation, such as trophoblast migration and spiral artery remodeling, and trophoblast sensing and response to infectious and noninfectious agents. Research findings in these areas will be critical for the formulation of the development of future treatments and the development of therapies for the prevention of a number of pregnancy disorders of placental origin that include preeclampsia, fetal growth restriction, and uterine inflammation. Research was also presented that summarized ongoing clinical efforts in the United States and in Europe that has tested novel interventions for preeclampsia and fetal growth restriction, including agents such as oral arginine supplementation, sildenafil, pravastatin, gene therapy with virally delivered vascular endothelial growth factor, and oxygen supplementation therapy. Strategies were also proposed to improve fetal growth by the enhancement of nutrient transport to the fetus by modulation of their placental transporters and the targeting of placental

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

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

    2012-01-01

    Many human diseases share a developmental origin that manifests during childhood or maturity. Aneuploid syndromes are caused by supernumerary or reduced number of chromosomes and represent an extreme example of developmental disease, as they have devastating consequences before and after birth. Investigating how alterations in gene dosage drive these conditions is relevant because it might help treat some clinical aspects. It may also provide explanations as to how quantitative differences in gene expression determine phenotypic diversity and disease susceptibility among natural populations. Here, we aimed to produce induced pluripotent stem cell (iPSC) lines that can be used to improve our understanding of aneuploid syndromes. We have generated iPSCs from monosomy X [Turner syndrome (TS)], trisomy 8 (Warkany syndrome 2), trisomy 13 (Patau syndrome) and partial trisomy 11;22 (Emanuel syndrome), using either skin fibroblasts from affected individuals or amniocytes from antenatal diagnostic tests. These cell lines stably maintain the karyotype of the donors and behave like embryonic stem cells in all tested assays. TS iPSCs were used for further studies including global gene expression analysis and tissue-specific directed differentiation. Multiple clones displayed lower levels of the pseudoautosomal genes ASMTL and PPP2R3B than the controls. Moreover, they could be transformed into neural-like, hepatocyte-like and heart-like cells, but displayed insufficient up-regulation of the pseudoautosomal placental gene CSF2RA during embryoid body formation. These data support that abnormal organogenesis and early lethality in TS are not caused by a tissue-specific differentiation blockade, but rather involves other abnormalities including impaired placentation. PMID:21949351

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

    O. I. Stepanova; G. R. Kozonov; D. Z. Tsitskarava; T. U. Kuzminykh; D. A. Korenkov; S. A. Selkov; D. I. Sokolov

    2014-01-01

    Decidual and placental macrophage pools are renewed due to its transendothelial monocyte migration from peripheral blood. Tissue macrophages control placental development and provide fetomaternal immunological tolerance. Preeclamptic pregnancy is accompanied by increased monocyte migration to decidual tissue and local inflammatory events. Regulatory mechanisms of monocyte recruitment to placental and decidual tissues is still unclear. Therefore we investigated the influence soluble placental ...

  5. Placental Hypoxia Developed During Preeclampsia Induces Telocytes Apoptosis in Chorionic Villi Affecting The Maternal-Fetus Metabolic Exchange.

    Bosco, Cleofina Becerra; Díaz, Eugenia Guerra; Gutierrez, Rodrigo Rojas; González, Jaime Montero; Parra-Cordero, Mauro; Rodrigo, Ramón Salinas; Barja, Pilar Yañez

    2016-01-01

    Telocytes (TC) are a new type of stromal cells initially found and studied in digestive and extra- digestive organs. These cells have a small cell body with 2 to 5 thin and extremely long cytoplasmic prolongations named telopodes. In recent years, TC have also been described in placental chorionic villi, located in a strategical position between the smooth muscle cells from fetal vessels and the myofibroblasts in the stromal villi. Unlike other organs, the placenta is not innervated and considering the strategic location of TC is has been postulated that TC function would be related to signal transduction mechanisms involved in the regulation of the fetal vessels blood flow, as well as in the shortening/lengthening of the chorionic villi, providing the necessary rhythmicity to the process of maternal/fetal metabolic exchange. Preeclampsia (PE) is a systemic syndrome that affects 4%-6% of pregnancies worldwide. It is characterized by a placental state of ischemia-hypoxia which triggers an oxidative stress stage with the concomitant production of reactive oxygen species (ROS) leading to an increase in the degree of placental apoptosis. Placental vascular tone is regulated by the vasodilator nitric oxide (NO) and, in PE cases, NO is diverted towards the formation of peroxynitrite, a powerful oxidative agent whose activity leads to an increase of placental apoptosis degree that compromises TC and myofibroblasts, a key feature we would like to emphasize in this work. PMID:25643124

  6. Placental perfusion - a human alternative

    Mose, Tina; Knudsen, Lisbeth E

    2006-01-01

    Foetal exposures to environmental and medicinal products have impact on the growth of the foetus (e.g. cigarette smoke) and development of organs (e.g. methylmercury and Thalidomide). Perfusion studies of the human term placenta enable investigation of placental transport of chemical substances...... part of work package 2 of the integrated project ReProTect....

  7. Development of Abnormality Detection System for Bathers using Ultrasonic Sensors

    Ohnishi, Yosuke; Abe, Takehiko; Nambo, Hidetaka; Kimura, Haruhiko; Ogoshi, Yasuhiro

    This paper proposes an abnormality detection system for bather sitting in bathtub. Increasing number of in-bathtub drowning accidents in Japan draws attention. Behind this large number of bathing accidents, Japan's unique social and cultural background come surface. For majority of people in Japan, bathing serves purpose in deep warming up of body, relax and enjoyable time. Therefore it is the custom for the Japanese to soak in bathtub. However overexposure to hot water may cause dizziness or fainting, which is possible to cause in-bathtub drowning. For drowning prevention, the system detects bather's abnormal state using an ultrasonic sensor array. The array, which has many ultrasonic sensors, is installed on the ceiling of bathroom above bathtub. The abnormality detection system uses the following two methods: posture detection and behavior detection. The function of posture detection is to estimate the risk of drowning by monitoring bather's posture. Meanwhile, the function of behavior detection is to estimate the risk of drowning by monitoring bather's behavior. By using these methods, the system detects bathers' different state from normal. As a result of experiment with a subject in the bathtub, the system was possible to detect abnormal state using subject's posture and behavior. Therefore the system is useful for monitoring bather to prevent drowning in bathtub.

  8. Decreasing maternal nutrient intake during the final third of pregnancy in previously overnourished adolescent sheep: effects on maternal nutrient partitioning and feto-placental development.

    Redmer, D A; Milne, J S; Aitken, R P; Johnson, M L; Borowicz, P P; Reynolds, L P; Caton, J S; Wallace, J M

    2012-02-01

    When pregnant adolescent sheep are overnourished during pregnancy normal nutrient partitioning priorities to the gravid uterus are altered, leading to impaired placental development and fetal growth restriction. We hypothesized that decreasing dietary intake in overnourished dams during the final third of gestation may reverse this inappropriate nutrient partitioning in favor of the fetus. Adolescent ewes were offered control (C; n = 12) or high (H; n = 20) dietary intakes to induce normal vs. compromised placental development. Ten ewes receiving the H intake were switched to a low intake at d90 of gestation (HL). Between d90 to 130, HL dams lost weight and adiposity, and metabolic hormones and glucose at d130 were less than H and similar to C. In spite of these maternal changes, at d130 fetal bodyweight was equivalent in HL and H groups and ∼20% less than in C. A greater degree of brain sparing was evident in HL fetuses and glucose and insulin concentrations were more perturbed than in H fetuses. Relative to C, placentome weight was reduced by 46 and 32% in H and HL and the fetal:placentome weight ratio was H > HL > C. Placental vascular morphology was largely unaffected by maternal diet during late gestation but mRNA expression of five angiogenic genes was up-regulated in the fetal cotyledon of HL pregnancies, commensurate with blood vessel remodeling. Nevertheless, overfeeding to promote maternal anabolic growth during adolescent pregnancy impairs feto-placental development that cannot be rescued by reducing maternal intake during the final third of gestation. PMID:22154692

  9. A disintegrin and metalloproteinase 12 (ADAM12) localizes to invasive trophoblast, promotes cell invasion and directs column outgrowth in early placental development.

    Aghababaei, M; Perdu, S; Irvine, K; Beristain, A G

    2014-03-01

    During pregnancy, stromal- and vascular-remodeling trophoblasts serve critical roles in directing placental development acquiring pro-invasive characteristics. The A Disintegrin and Metalloproteinase (ADAM) family of multifunctional proteins direct cellular processes across multiple organ systems via their intrinsic catalytic, cell adhesive and intracellular signaling properties. ADAM12, existing as two distinct splice variants (ADAM12L and ADAM12S), is highly expressed in the human placenta and promotes cell migration and invasion in several tumor cell lines; however, its role in trophoblast biology is unknown. In this study, ADAM12 was localized to anchoring trophoblast columns in first trimester placentas and to highly invasive extracellular matrix-degrading trophoblasts in placental villous explants. The importance of ADAM12 in directing trophoblast invasion was tested using loss-of and gain-of-function strategies, where siRNA-directed knockdown of ADAM12 inhibited trophoblast cell invasion while over-expression promoted migration and invasion in two trophoblastic cell models. In placental villous explant cultures, siRNA-directed loss of ADAM12 significantly dampened trophoblast column outgrowth. Additionally, we provide functional evidence for the ADAM12S variant in promoting trophoblast invasion and column outgrowth through a mechanism requiring its catalytic activity. This is the first study to assign a function for ADAM12 in trophoblast biology, where ADAM12 may play a central role regulating the behavior of invasive trophoblast subsets in early pregnancy. This study also underlines the importance of ADAM12L and ADAM12S in directing cell motility in normal developmental processes outside of cancer, specifically highlighting a potentially important function of ADAM12S in directing early placental development. PMID:24243624

  10. Placental Adaptations in Growth Restriction

    Song Zhang

    2015-01-01

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

  11. Animal Models of Human Placentation - A Review

    Carter, Anthony Michael

    2007-01-01

    This review examines the strengths and weaknesses of animal models of human placentation and pays particular attention to the mouse and non-human primates. Analogies can be drawn between mouse and human in placental cell types and genes controlling placental development. There are, however...... is no trophoblast invasion of uterine vessels, and the immunology of pregnancy may be quite different. We conclude that continued research on non-human primates is needed to clarify embryonic-endometrial interactions. The interstitial implantation of human is unusual, but the initial interaction...... and delivers poorly developed young. Guinea pig is a good alternative rodent model and among the few species known to develop pregnancy toxaemia. The sheep is well established as a model in fetal physiology but is of limited value for placental research. The ovine placenta is epitheliochorial, there...

  12. The Role of PTHrP in Murine Placental Development and Function

    Duval, Chloe

    2014-01-01

    Parathyroid hormone-related peptide (PTHrP) is abundantly expressed throughout the gestational tissues and has multiple roles in fetal development. The importance of PTHrP in embryonic growth and survival is emphasised by the retarded growth and peri-natal lethality of the PTHrP knockout mouse. PTHrP is a regulator of cell survival, proliferation and differentiation in a number of tissues and organs. However, its effects in the development and function of the placenta are yet to be fully defi...

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

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

    2015-12-01

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

  14. Constitutive Notch Signaling Causes Abnormal Development of the Oviducts, Abnormal Angiogenesis, and Cyst Formation in Mouse Female Reproductive Tract.

    Ferguson, Lydia; Kaftanovskaya, Elena M; Manresa, Carmen; Barbara, Agustin M; Poppiti, Robert J; Tan, Yingchun; Agoulnik, Alexander I

    2016-03-01

    The Notch signaling pathway is critical for the differentiation of many tissues and organs in the embryo. To study the consequences of Notch1 gain-of-function signaling on female reproductive tract development, we used a cre-loxP strategy andAmhr2-cretransgene to generate mice with conditionally activated Notch1 (Rosa(Notch1)). TheAmhr2-cretransgene is expressed in the mesenchyme of developing female reproductive tract and in granulosa cells in the ovary. Double transgenicAmhr2-cre, Rosa(Notch1)females were infertile, whereas controlRosa(Notch1)mice had normal fertility. All female reproductive organs in mutants showed hemorrhaging of blood vessels progressing with age. The mutant oviducts did not develop coiling, and were instead looped around the ovary. There were multiple blockages in the lumen along the oviduct length, creating a barrier for sperm or oocyte passage. Mutant females demonstrated inflamed uteri with increased vascularization and an influx of inflammatory cells. Additionally, older females developed ovarian, oviductal, and uterine cysts. The significant change in gene expression was detected in the mutant oviduct expression ofWnt4, essential for female reproductive tract development. Similar oviductal phenotypes have been detected previously in mice with activatedSmoand inbeta-catenin,Wnt4,Wnt7a, andDicerconditional knockouts, indicating a common regulatory pathway disrupted by these genetic abnormalities. PMID:26843448

  15. Placental Origins of Chronic Disease.

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

    2016-10-01

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

  16. The distinct proteome of placental malaria parasites.

    Fried, Michal; Hixson, Kim K.; Anderson, Lori; Ogata, Yuko; Mutabingwa, Theonest K.; Duffy, Patrick E.

    2007-09-01

    Malaria proteins expressed on the surface of Plasmodium falciparum infected erythrocytes (IE) mediate adhesion and are targeted by protective immune responses. During pregnancy, IE sequester in the placenta. Placental IE bind to the molecule chondroitin sulfate A (CSA) and preferentially transcribe the gene that encodes VAR2CSA, a member of the PfEMP1 variant surface antigen family. Over successive pregnancies women develop specific immunity to CSA-binding IE and antibodies to VAR2CSA. We used tandem mass spectrometry together with accurate mass and time tag technology to study IE membrane fractions of placental parasites. VAR2CSA peptides were detected in placental IE and in IE from children, but the MC variant of VAR2CSA was specifically associated with placental IE. We identified six conserved hypothetical proteins with putative TM or signal peptides that were exclusively expressed by the placental IE, and 11 such proteins that were significantly more abundant in placental IE. One of these hypothetical proteins, PFI1785w, is a 42kDa molecule detected by Western blot in parasites infecting pregnant women but not those infecting children.

  17. Sirh7/Ldoc1 knockout mice exhibit placental P4 overproduction and delayed parturition

    Naruse, Mie; Ono, Ryuichi; Irie, Masahito; Nakamura, Kenji; Furuse, Tamio; Hino, Toshiaki; Oda, Kanako; Kashimura, Misho; Yamada, Ikuko; Wakana, Shigeharu; Yokoyama, Minesuke; Ishino, Fumitoshi; Kaneko-Ishino, Tomoko

    2014-01-01

    Sirh7/Ldoc1 [sushi-ichi retrotransposon homolog 7/leucine zipper, downregulated in cancer 1, also called mammalian retrotransposon-derived 7 (Mart7)] is one of the newly acquired genes from LTR retrotransposons in eutherian mammals. Interestingly, Sirh7/Ldoc1 knockout (KO) mice exhibited abnormal placental cell differentiation/maturation, leading to an overproduction of placental progesterone (P4) and placental lactogen 1 (PL1) from trophoblast giant cells (TGCs). The placenta is an organ tha...

  18. Abnormal embryonic lymphatic vessel development in Tie1 hypomorphic mice

    Qu, Xianghu; Tompkins, Kevin; Batts, Lorene E.; Puri, Mira; Baldwin, H. Scott

    2010-01-01

    Tie1 is an endothelial receptor tyrosine kinase that is essential for development and maintenance of the vascular system; however, the role of Tie1 in development of the lymphatic vasculature is unknown. To address this question, we first documented that Tie1 is expressed at the earliest stages of lymphangiogenesis in Prox1-positive venous lymphatic endothelial cell (LEC) progenitors. LEC Tie1 expression is maintained throughout embryonic development and persists in postnatal mice. We then ge...

  19. Normal and Abnormal Embryonic Development in Virtual Reality

    L. Baken (Leonie)

    2014-01-01

    markdownabstract__Abstract__ Research of the past years indicates that the periconception period, the period including gametogenesis and embryogenesis, determines growth and development of the embryo and subsequent pregnancy outcome. Prenatal care starts to focus more on the first-trimester of preg

  20. Linear scleroderma en coup de sabre including abnormal dental development

    Hørberg, M; Lauesen, S R; Daugaard-Jensen, J; Kjær, I

    2015-01-01

    of eruption. FOLLOW-UP: The patient has been regularly controlled and treated since she was first diagnosed. A surgical and orthodontic treatment was performed to ensure optimal occlusion, space and alveolar bone development. The present age of the patient is 14 years and 10 months. CONCLUSION: This...

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

    Higgins Michael J

    2010-05-01

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

  2. Maternal environment and placental vascularization in small ruminants.

    Bairagi, S; Quinn, K E; Crane, A R; Ashley, R L; Borowicz, P P; Caton, J S; Redden, R R; Grazul-Bilska, A T; Reynolds, L P

    2016-07-01

    Uteroplacental development is a crucial step facilitating conceptus growth. Normal placental development comprises extensive placental angiogenesis to support fetoplacental transport, meeting the metabolic demands of the fetus. Compromised pregnancies due to maternal stressors such as over or undernutrition, maternal age or parity, altered body mass index, or genetic background result in altered vascular development of the placenta. This negatively affects placental growth and placental function and ultimately results in poor pregnancy outcomes. Nonetheless, the placenta acts as a sensor to the maternal stressors and undergoes modifications, which some have termed placental programming, to ensure healthy development of the conceptus. Sex steroid hormones such as estradiol-17β and progesterone, chemokines such as chemokine ligand 12, and angiogenic/vasoactive factors such as vascular endothelial growth factors, placental growth factor, angiopoietins, and nitric oxide regulate uteroplacental development and hence are often used as therapeutic targets to rescue compromised pregnancies. Interestingly, the presence of sex steroid receptors has been identified in the fetal membranes (developing fetal placenta). Environmental steroid mimetics known as endocrine disrupting compounds disrupt conceptus development and lead to transgenerational impairments by epigenetic modification of placental gene expression, which is another area deserving intense research efforts. This review attempts to summarize current knowledge concerning intrinsic and extrinsic factors affecting selected reproductive functions with the emphasis on placental development. PMID:27173956

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

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

    2016-03-01

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

  4. X chromosome abnormalities and cognitive development: implications for understanding normal human development.

    Walzer, S

    1985-03-01

    Recent advances in the biological sciences have offered new opportunities to identify biological contributions as they interact with social experience to help determine psychological development. The role of biological factors is more easily demonstrated in subhuman species in which extensive experimental manipulations of variables are possible. One strategy for the study of human behaviour genetics has been the systematic analysis of behaviour in individuals with naturally occurring X chromosome variations. The aim has been to demonstrate whether or not the range of expected variability in particular areas of behavioural development was narrowed by the specific genotypic abnormality. The knowledge obtained from these studies can be applied meaningfully to enhance our understanding about human behavioural development in chromosomally unaffected individuals. PMID:3884639

  5. The feto-placental unit, and potential roles of dehydroepiandrosterone (DHEA) in prenatal and postnatal brain development: A re-examination using the spiny mouse.

    Quinn, Tracey A; Ratnayake, Udani; Dickinson, Hayley; Castillo-Melendez, Margie; Walker, David W

    2016-06-01

    Synthesis of dehydroepiandrosterone (DHEA) by the fetal adrenal gland is important for placental oestrogen production, and may also be important for modulating the effects of glucocorticoids on the developing brain. We have preciously shown that the enzymes and accessory proteins needed for DHEA synthesis-cytochrome P450 enzyme 17α-hydroxylase/17,20 lyase (P450c17), cytochrome-b5 (Cytb5), 3β-hydroxysteroid dehydrogenase (3βHSD)-are expressed in the adrenal gland from 30 days gestation, and DHEA, cortisol and aldosterone are present in fetal plasma from this time. Explant culture of fetal adrenal tissue showed that the spiny mouse adrenal gland, can synthesize and secrete DHEA from at least 0.75 of gestation, and suggest that DHEA may have an important role(s) in placental biosynthesis of oestrogens and in modulating the actions of glucocorticoids in the developing brain in this species. Post-natally, increased immuno-expression of P450c17 and Cytb5 expression in the zona reticularis of the adrenal gland and a significant increase in the synthesis and secretion of DHEA in plasma from 8 to 20 days of age in the spiny mouse, are representative of a period of high adrenal androgen production consistent with the human phenomenon of adrenarche. The studies summarised in this review also show that DHEA is produced de novo in the developing brain of the spiny mouse. These results showed that the spiny mouse brain can indeed produce DHEA from pregnenolone in a time-dependant manner, and coupled with the identification of P450c17 and Cytb5 protein in several regions of the brain, support the idea that DHEA is an endogenous neuro-active steroid in this species. Together, the studies outlined in this review indicate that the androgen DHEA is an important hormone of adrenal and Central Nervous System (CNS) origin in the fetal and postnatal spiny mouse. Disturbance of the development of these fetal tissues, and/or of the relationship between the fetal adrenal gland and

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

    Phelps, William R.

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

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

    Chung-Wei Yang

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

  8. The embryonic development of ear-tufts and associated structural head and neck abnormalities of the Araucana fowl.

    Pabilonia, M S; Somes, R G

    1983-08-01

    Developing embryonic structural abnormalities of ear-tufted embryos of the Araucana fowl are described. These abnormal structures are peduncle, cleft, ear opening, tympanic membrane, and columella auris. The structural abnormalities are believed to be due to the early incomplete fusion of the hyoid and mandibular arches from the distal part of the ear opening to the neck area. PMID:6634592

  9. Ascending placentitis in the mare: A review

    Cummins C

    2008-05-01

    Full Text Available Abstract Ascending placentitis is a condition that occurs late in pregnancy when bacteria enter the sterile uterus from the lower reproductive tract. It leads to abortion or the birth of premature and weakened foals. Early detection and treatment of this condition is vital for ensuring the production of a viable foal. Mares with ascending placentitis often present in late term pregnancy with signs of premature udder development and premature lactation. There may be a vulvar discharge. Early detection of placental problems is possible using trans-abdominal or trans-rectal ultrasonography. Hormones such as progesterone and relaxin may be measured as indicators of foetal stress and placental failure. Postpartum foetal membranes may be thickened and contain a fibronecrotic exudate. The region most affected is the cervical star. Definitive diagnosis of ascending placentitis is by histopathological examination of the chorioallantoic membrane. Ideal treatment strategies are aimed at curing the infection and prolonging the pregnancy to as close to term as possible and consist of anti-microbials, anti-inflammatories and hormonal support. Swabs are taken from affected mares to determine antibiotic sensitivity and to aid in treatment of foals born from these mares which are at risk of becoming septic. If detected early enough, the chances of producing a viable foal are greatly increased.

  10. Ascending placentitis in the mare: A review.

    Cummins, C; Carrington, S; Fitzpatrick, E; Duggan, V

    2008-01-01

    Ascending placentitis is a condition that occurs late in pregnancy when bacteria enter the sterile uterus from the lower reproductive tract. It leads to abortion or the birth of premature and weakened foals. Early detection and treatment of this condition is vital for ensuring the production of a viable foal.Mares with ascending placentitis often present in late term pregnancy with signs of premature udder development and premature lactation. There may be a vulvar discharge. Early detection of placental problems is possible using trans-abdominal or trans-rectal ultrasonography. Hormones such as progesterone and relaxin may be measured as indicators of foetal stress and placental failure. Postpartum foetal membranes may be thickened and contain a fibronecrotic exudate. The region most affected is the cervical star. Definitive diagnosis of ascending placentitis is by histopathological examination of the chorioallantoic membrane.Ideal treatment strategies are aimed at curing the infection and prolonging the pregnancy to as close to term as possible and consist of anti-microbials, anti-inflammatories and hormonal support.Swabs are taken from affected mares to determine antibiotic sensitivity and to aid in treatment of foals born from these mares which are at risk of becoming septic. If detected early enough, the chances of producing a viable foal are greatly increased. PMID:21851713

  11. Macrophage Exosomes Induce Placental Inflammatory Cytokines: A Novel Mode of Maternal-Placental Messaging.

    Holder, Beth; Jones, Tessa; Sancho Shimizu, Vanessa; Rice, Thomas F; Donaldson, Beverly; Bouqueau, Marielle; Forbes, Karen; Kampmann, Beate

    2016-02-01

    During pregnancy, the placenta forms the interface between mother and fetus. Highly controlled regulation of trans-placental trafficking is therefore essential for the healthy development of the growing fetus. Extracellular vesicle-mediated transfer of protein and nucleic acids from the human placenta into the maternal circulation is well documented; the possibility that this trafficking is bi-directional has not yet been explored but could affect placental function and impact on the fetus.We hypothesized that the ability of the placenta to respond to maternal inflammatory signals is mediated by the interaction of maternal immune cell exosomes with placental trophoblast. Utilizing the BeWo cell line and whole placental explants, we demonstrated that the human placenta internalizes macrophage-derived exosomes in a time- and dose-dependent manner. This uptake was via clathrin-dependent endocytosis. Furthermore, macrophage exosomes induced release of proinflammatory cytokines by the placenta. Taken together, our data demonstrates that exosomes are actively transported into the human placenta and that exosomes from activated immune cells modulate placental cytokine production. This represents a novel mechanism by which immune cells can signal to the placental unit, potentially facilitating responses to maternal inflammation and infection, and thereby preventing harm to the fetus. PMID:26602702

  12. Study of correlation between perinatal outcome, placental coefficient and feto-placental ratio

    Manik Sirpurkar

    2015-04-01

    Full Text Available Background: Pregnancy and birth are nature's finest marvel wherein perfect symbiosis between the two individuals protects the little and weak one and also allows the propagation of genetic prototype of the other individual generation after generation. Placenta acts as a mirror which reflects intrauterine status of fetus. Placenta has an undisputed role in foetal development but still is grossly neglected organ which is equal to liver, lung and kidney in function. Methods: Placentae collected from labor rooms and operation theatres were studied for various parameters like weight, surface area, volume, area of calcification and infarction, number of cotyledons etc. Birth weight of babies was also noted, feto-placental weight ratio and placental coefficient was calculated. Results: Average placental weight being 490.5 gm (range 295-660 gm. Placenta of male baby was found to be slightly heavier as compared to female babies. Birth weight of male babies was also more than female babies. Average placental surface area was found to be 225.5 sq. cm. Mean placental volume was recorded as 450.5 cu. cm. Foeto-placental weight ratio was found to be 5.41:1 irrespective of sex of the baby, 5.61:1 in case of male baby and 5.40:1 for female babies. Conclusion: The placenta is a mirror which reflects intrauterine status of the fetus. [Int J Res Med Sci 2015; 3(4.000: 925-928

  13. Placentation in mammals

    Carter, A M; Enders, A C

    2016-01-01

    An overview is given of variations in placentation with particular focus on yolk sac, paraplacenta, and other structures important to histotrophic nutrition. The placenta proper varies in general shape, internal structure, and the number of tissues in the interhemal barrier. Yolk sac membranes...

  14. Association of Traditional Cardiovascular Risk Factors With Development of Major and Minor Electrocardiographic Abnormalities: A Systematic Review.

    Healy, Caroline F; Lloyd-Jones, Donald M

    2016-01-01

    Electrocardiographic (ECG) abnormalities are prevalent in middle aged and are associated with risk of adverse cardiovascular events. It is unclear whether and to what extent traditional risk factors are associated with the development of ECG abnormalities. To determine whether traditional cardiovascular risk factors are associated with the presence or development of ECG abnormalities, we performed a systematic review of the English-language literature for cross-sectional and prospective studies examining associations between traditional cardiovascular risk factors and ECG abnormalities, including major and minor ECG abnormalities, isolated nonspecific ST-segment and T-wave abnormalities, other ST-segment and T-wave abnormalities, QT interval, Q waves, and QRS duration. Of the 202 papers initially identified, 19 were eligible for inclusion. We examined data analyzing risk factor associations with ECG abnormalities in individuals free of cardiovascular disease. For composite major or minor ECG abnormalities, black race, older age, higher blood pressure, use of antihypertensive medications, higher body mass index, diabetes, smoking, and evidence of left ventricular hypertrophy or higher left ventricular mass are the factors most commonly associated with prevalence and incidence. Risk factor associations differ somewhat according to types of specific ECG abnormalities. Because major and minor ECG abnormalities have important and independent prognostic significance, understanding the groups at risk for their development may inform prevention strategies focused on modifiable risk factors to reduce the burden of ECG abnormalities, which may in turn promote CVD prevention. PMID:27054606

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

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

    2016-01-01

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

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

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

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

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

    2001-02-01

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

  18. Co-culture of placental explants with isolated CD4 and CD8 T cells: a functional model to define the consequences of placental inflammation

    Hayley Derricott

    2015-11-01

    Full Text Available Appropriate placental function is essential for successful pregnancy and placental dysfunction is associated with fetal growth restriction (FGR and stillbirth. Villitis of unknown etiology (VUE and chronic intervillositis of unknown etiology (CIUE are immune-mediated conditions characterised by placental infiltrates of macrophages, CD4 and CD8 T cells. VUE and CIUE occur more frequently in the placentas of pregnancies complicated by FGR. The mechanisms by which this inflammation induces placental dysfunction are yet to be defined. We aimed to develop an in vitro model of placental inflammation to investigate functional consequences of immune cells in the placental environment. Fragments of placental tissue were co-cultured with CD4 and CD8 T cells isolated from whole blood. CellTrackerTM fluorescence was used to identify T cells in cultured explants. Tissue histology, endocrine and nutrient transport function was assessed using established methods. This novel preparation will enable future investigations into immune cell interactions with placenta.

  19. Umbillical venous volume inflow and liver size in normal and abnormal fetal development

    S.M. Boito

    2003-01-01

    textabstractIn this thesis the following research objectives were addressed: To calculate umbilical venous volume flow from cross-sectional area and flow velocity measurements with emphasis on: (i) the reproducibility of component measurements; (ii) normal and abnormal fetal development, the latter

  20. Ethical aspects of banking placental blood for transplantation.

    Sugarman, J; Reisner, E G; Kurtzberg, J

    1995-12-13

    Transplantation of blood cells harvested from the umbilical cord immediately after birth has been effective in repopulating the bone marrow. These placental blood transplantations may be safer than conventional bone marrow transplantations and may suspend the need to harvest bone marrow, a process fraught with difficulties. Further understanding and advancement of this emerging technology require developing large banks of placental blood. In this article, we examine some of the ethical issues associated with placental blood banking, including (1) questions about ownership of the tissue, (2) the necessity and nature of obtaining informed consent from parents for harvesting placental blood and the information-gathering process associated with it, (3) obligations to notify parents and children of the results of medical testing for infectious diseases and genetic information, (4) matters of privacy and confidentiality related to such information, and (5) the need for fair and equitable harvesting of and access to placental blood. PMID:7500510

  1. Understanding normal and abnormal development of the Wolffian/epididymal duct by using transgenic mice.

    Murashima, Aki; Xu, Bingfang; Hinton, Barry T

    2015-01-01

    The development of the Wolffian/epididymal duct is crucial for proper function and, therefore, male fertility. The development of the epididymis is complex; the initial stages form as a transient embryonic kidney; then the mesonephros is formed, which in turn undergoes extensive morphogenesis under the influence of androgens and growth factors. Thus, understanding of its full development requires a wide and multidisciplinary view. This review focuses on mouse models that display abnormalities of the Wolffian duct and mesonephric development, the importance of these mouse models toward understanding male reproductive tract development, and how these models contribute to our understanding of clinical abnormalities in humans such as congenital anomalies of the kidney and urinary tract (CAKUT). PMID:26112482

  2. Maternal Serum Analytes as Predictors of Fetal Growth Restriction with Different Degrees of Placental Vascular Dysfunction.

    Blitz, Matthew J; Rochelson, Burton; Vohra, Nidhi

    2016-06-01

    Abnormal levels of maternal serum analytes have been associated with fetal growth restriction (FGR) and preeclampsia secondary to placental vascular dysfunction. Accurately identifying the FGR fetuses at highest risk for adverse outcomes remains challenging. Placental function can be assessed by Doppler analysis of the maternal and fetal circulation. Although the combination of multiple abnormal maternal serum analytes and abnormal Doppler findings is strongly associated with adverse outcomes, the predictive value remains too low to be used as a screening test in a low-risk population. Stratification of cases based on the severity of Doppler abnormalities may improve predictive models. PMID:27235917

  3. Placental toxicology: tobacco smoke, abused drugs, multiple chemical interactions, and placental function.

    Sastry, B V

    1991-01-01

    There are increasing numbers of reports on the tobacco smoking and ingestion of abused drugs (e.g. morphine, cocaine) by pregnant women and the effects of the substances on the developing fetus and newborn infant. The passage of drugs and chemicals from the mother to the fetus is influenced by the placental transport and metabolism of the substances. Further, these drugs and chemicals affect the nutrient transport systems in the placenta. The three major drugs of abuse-nicotine, morphine and cocaine-depress both active amino-acid uptake by human placental villi and transplacental amino-acid transport by reason of the drugs' influence on placental cholinergic and opiate systems. Part of this depression (10-16%) is not reversible. Nicotine blocks the cholinergic receptor and thus blocks acetylcholine (ACh)-facilitated amino-acid transport. Morphine stimulates opiate kappa receptors and depresses ACh release. Cocaine blocks Ca2+ influx and thus blocks ACh release. ACh causes dilation of blood vessels and maintains placental blood flow by the activation of endothelial muscarinic receptors. By interfering with ACh release and placental blood flow, the three drugs of abuse may depress the diffusion of amino acids and other nutrients from the trophoblast into the placental circulation. Three regulatory systems are delineated for amino-acid uptake by the placenta: placental ACh, phospholipid N-methyltransferase, and the gammaglutamyl cycle. These systems operate in concert with one another and are dependent on cellular formation of adenosine 5'-triphosphate (ATP). Placental hypoxia induced by carbon monoxide and other tobacco gases depresses the energy-dependent processes and thus the ATP levels of placental cells. Maternal tobacco smoking and drug abuse cause placental insufficiencies for amino-acid transport, which may partially explain the fetal intrauterine growth retardation caused by these substances. Part of the amino-acid deficits may be compensated for by the

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

    Yi Liu

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

  5. A RADIOIMMUNOASSAY FOR PLACENTAL PROTEIN PP5

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

    1989-01-01

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

  6. Embryonic exposures of lithium and homocysteine and folate protection affect lipid metabolism during mouse cardiogenesis and placentation.

    Han, Mingda; Evsikov, Alexei V; Zhang, Lifeng; Lastra-Vicente, Rosana; Linask, Kersti K

    2016-06-01

    Embryonic exposures can increase the risk of congenital cardiac birth defects and adult disease. The present study identifies the predominant pathways modulated by an acute embryonic mouse exposure during gastrulation to lithium or homocysteine that induces cardiac defects. High dose periconceptional folate supplementation normalized development. Microarray bioinformatic analysis of gene expression demonstrated that primarily lipid metabolism is altered after the acute exposures. The lipid-related modulation demonstrated a gender bias with male embryos showing greater number of lipid-related Gene Ontology biological processes altered than in female embryos. RT-PCR analysis demonstrated significant change of the fatty acid oxidation gene Acadm with homocysteine exposure primarily in male embryos than in female. The perturbations resulting from the exposures resulted in growth-restricted placentas with disorganized cellular lipid droplet distribution indicating lipids have a critical role in cardiac-placental abnormal development. High folate supplementation protected normal heart-placental function, gene expression and lipid localization. PMID:26993217

  7. Pathogens and the Placental Fortress

    Robbins, Jennifer R.; Anna I Bakardjiev

    2011-01-01

    Placental infections are major causes of maternal and fetal disease. This review introduces a new paradigm for placental infections based on current knowledge of placental defenses and how this barrier can be breached. Transmission of pathogens from mother to fetus can occur at two sites of direct contact between maternal cells and specialized fetal cells (trophoblasts) in the human placenta: (i) maternal immune and endothelial cells juxtaposed to extravillous trophoblasts in the uterine impl...

  8. Placental Tumour: What could it be?

    Al-Riyami, Nihal; Al-Hadabi, Rahma; Al-Dughaishi, Tamima; Al-Riyami, Marwa

    2013-01-01

    Placental tumours include placental chorioangiomas, teratomas, haemangiomas, and haematomas. Placental chorioangiomas are benign vascular tumours and are the most common placental tumours, with a prevalence of 1%. Large placental chorioangiomas are rare and may lead to pregnancy complications and poor perinatal outcomes. These complications include fetal anaemia, hydrops fetalis, fetal growth restriction, polyhydramnios, and preterm delivery. We report a case of a large placental chorioangiom...

  9. Normal and abnormal fetal brain development during the third trimester as demonstrated by neurosonography

    The multiplanar neurosonographic examination of the fetus enables superb visualization of brain anatomy during pregnancy. The examination may be performed using a transvaginal or a transfundal approach and it is indicated in patients at high risk for CNS anomalies or in those with a suspicious finding during a routine examination. The purpose of this paper is to present a description of the normal brain and of abnormal findings usually diagnosed late in pregnancy, including malformations of cortical development, infratentorial anomalies, and prenatal insults

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

    Lucarelli Elisabetta

    2011-04-01

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

  11. Development of an induction motor abnormality monitoring system(IMAMS) using power line signal analysis

    An induction motor abnormality monitoring system using power line signal analysis is developed in this work. Various studies have focused their attention on the detection of particular harmonic frequencies produced from each defect mode of motors. However, these harmonic frequencies are valuable only when the motor has a continuous slip frequency and operate in constant torque/load condition. The basic concept of the system developed in this work is to detect the characteristic harmonic frequencies occurred when the motor is in abnormal state and to compare it with a predetermined setpoint. Based on these analyses, the place and degree of defect can be easily identified. The experimental results under test bench simulation are also introduced. To find out an alternative way to obtain a threshold level independent of slip/torque, with the rotating field theory, the ratio between harmonic current and total current was calculated with the simplified circuit that is equivalent to two abnormal cases, such as the spatial rotor resistance variation and the symmetrical components changes with field. Also, the threshold level calculation was done with performed the rotating field theory. The results show that they are in good agreement with a experimental results. Further studies are undertaken to extend this work to the on-line monitoring and diagnostic system with a likelihood ratio test method for field application

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

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

    2016-02-01

    The aim of this study was to evaluate cytogenetic findings in Omani patients who had been referred for suspicion of sex chromosome abnormalities that resulted in different clinical disorders. Furthermore, it sought to examine the frequency of chromosomal anomalies in these patients and to compare the obtained results with those reported elsewhere. Cytogenetic analysis was performed on 1232 cases with variant characteristics of sexual development disorders who had been referred to the cytogenetic department, National Genetic Centre, Ministry of Health, from different hospitals in the Sultanate of Oman between 1999 and 2014. The karyotype results demonstrated chromosomal anomalies in 24.2% of the cases, where 67.5% of abnormalities were identified in referral females, whereas only 32.6% were in referral males. Of all sex chromosome anomalies detected, Turner syndrome was the most frequent (38.2%) followed by Klinefelter syndrome (24.9%) and XY phenotypic females (16%). XXX syndrome and XX phenotypic males represented 6.8% and 3.8% of all sex chromosome anomalies, respectively. Cytogenetic analysis of patients referred with various clinical suspicions of chromosomal abnormalities revealed a high rate of chromosomal anomalies. This is the first broad cytogenetic study reporting combined frequencies of sex chromosome anomalies in sex development disorders in Oman. PMID:26706459

  13. Improvement of the abnormal diagnosis technology by the development of an abnormal parts assignment system for the engineered safety features actuating system of the HTTR

    The safety protection sequence panel of HTTR is a control panel to actuate an engineering safety system for protecting the reactor core, reactor coolant pressure boundary, and containment vessel boundary at the time of an accident of the nuclear reactor facilities. The safety code stipulates that the control panel should receive safety check at a frequency of once a month during reactor operation. When abnormality has been found, it is required to eliminate its causes and restore normal operation as soon as possible. However, since this control panel is composed of a complex control circuit, the cause check during abnormality requires the confirmation by a knowledgeable person spending quite a lot of time for chart checking, which leads to a delay of restoration. To achieve a rapid restoration, the abnormal part assignment system (APAS), which can specify abnormality instantaneously even by a common operator, was developed. It has been confirmed that with this system, rapid initial response and prompt restoration can be effectively made. (A.O.)

  14. Role of placental nutrient sensing in developmental programming

    Jansson, Thomas; Powell, Theresa L.

    2013-01-01

    Altered maternal nutrition and metabolism, restricted utero-placental blood flow and other perturbations in the maternal compartment may disturb critical periods of fetal development resulting in increased susceptibility to develop disease in childhood and adult life. In response to these perturbations, placental structure and function changes, which influence the supply of nutrients, oxygen and methyl donors and alter the secretion of hormones and other signaling molecules into the fetal cir...

  15. Placental ischemia increases seizure susceptibility and cerebrospinal fluid cytokines.

    Warrington, Junie P

    2015-11-01

    Eclampsia is diagnosed in preeclamptic patients who develop unexplained seizures and/or coma during pregnancy or postpartum. Eclampsia is one of the leading causes of maternal and infant morbidity and mortality, accounting for ~13% of maternal deaths worldwide. Little is known about the mechanisms contributing to the pathophysiology of eclampsia, partly due to the lack of suitable animal models. This study tested the hypothesis that placental ischemia, induced by reducing utero-placental perfusion, increases susceptibility to seizures, cerebrospinal fluid (CSF) inflammation, and neurokinin B (NKB) expression in brain and plasma. Pentylenetetrazol (PTZ), a pro-convulsive drug, was injected into pregnant and placental ischemic rats (40 mg/kg, i.p.) on gestational day 19 followed by video monitoring for 30 min. Seizure scoring was blindly conducted. Placental ischemia hastened the onset of seizures compared to pregnant controls but had no effect on seizure duration. Placental ischemia increased CSF levels of IL-2, IL-17, IL-18 and eotaxin (CCL11), had no effect on plasma NKB; however, PTZ increased plasma NKB in both pregnant and placental ischemic rats. NKB was strongly correlated with latency to seizure in normal pregnant rats (R(2) = 0.88 vs. 0.02 in placental ischemic rats). Lastly, NKB decreased in the anterior cerebrum in response to placental ischemia and PTZ treatment but was unchanged in the posterior cerebrum. These data demonstrate that placental ischemia is associated with increased susceptibility to seizures and CSF inflammation; thus provides an excellent model for elucidating mechanisms of eclampsia-like symptoms. Further studies are required to determine the role of CSF cytokines/chemokines in mediating increased seizure susceptibility. PMID:26603461

  16. Ischemic placental syndrome - prediction and new disease monitoring.

    Kwiatkowski, Sebastian; Kwiatkowska, Ewa; Rzepka, Rafał; Torbe, Andrzej; Dolegowska, Barbara

    2016-06-01

    The last decade has seen an improved understanding of the cause of the development of pathologies such as gestational hypertension, preeclampsia, intrauterine growth restriction, intrauterine fetal death or placental abruption. Nowadays, we know that most conditions within this group share the same pathogenesis, the cause of which is placental ischemia. The following review is an attempt to propose a new method for prediction, diagnosis and - above all - appropriate monitoring of pregnant women and fetuses developing the ischemic placental syndrome with the use of tests that are new but yet widely available in clinical diagnosis. They are closely related to the condition's pathogenesis, therefore their elevated levels may predate clinical symptoms, and - most importantly - they correlate with syndrome aggravation and the occurrence of complications. Perhaps, the new look will allow us to improve perinatal results by reducing mortality and severe complications in pregnant women and fetal deaths resulting from sudden intrauterine fetal death or placental abruption. PMID:26444581

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

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

    2016-01-01

    Objective Systemic lupus erythematosus (SLE) is associated with increased risk of adverse pregnancy outcomes, including pre-eclampsia, particularly in association with antiphospholipid antibody syndrome (APS). While significant placental abnormalities are expected in pre-eclampsia, less is known about how lupus activity and APS in pregnancy affect the placenta. We describe placental pathology from a population of lupus pregnancies, several of which were complicated by APS-related thromboses, ...

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

    Horgan, R P

    2012-01-31

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

  19. Increased Placental Phospholipid Levels in Pre-Eclamptic Pregnancies

    Peter Bütikofer

    2013-02-01

    Full Text Available Physiological pregnancy is associated with an increase in lipids from the first to the third trimester. This is a highly regulated response to satisfy energy and membrane demands of the developing fetus. Pregnancy disorders, such as pre-eclampsia, are associated with a dysregulation of lipid metabolism manifesting in increased maternal plasma lipid levels. In fetal placental tissue, only scarce information on the lipid profile is available, and data for gestational diseases are lacking. In the present study, we investigated the placental lipid content in control versus pre-eclamptic samples, with the focus on tissue phospholipid levels and composition. We found an increase in total phospholipid content as well as changes in individual phospholipid classes in pre-eclamptic placental tissues compared to controls. These alterations could be a source of placental pathological changes in pre-eclampsia, such as lipid peroxide insult or dysregulation of lipid transport across the syncytiotrophoblast.

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

    Zhu, Xin-Xin; Li, Qiao-Yun; Shen, Chun-Cai; Duan, Zong-Biao; Yu, Dong-Yan; Niu, Ji-Shan; Ni, Yong-Jing; Jiang, Yu-Mei

    2016-01-01

    Background Wheat (Triticum aestivum L.) spike development is the foundation for grain yield. We obtained a novel wheat mutant, dms, characterized as dwarf, multi-pistil and sterility. Although the genetic changes are not clear, the heredity of traits suggests that a recessive gene locus controls the two traits of multi-pistil and sterility in self-pollinating populations of the medium plants (M), such that the dwarf genotype (D) and tall genotype (T) in the progeny of the mutant are ideal lines for studies regarding wheat spike development. The objective of this study was to explore the molecular basis for spike abnormalities of dwarf genotype. Results Four unigene libraries were assembled by sequencing the mRNAs of the super-bulked differentiating spikes and stem tips of the D and T plants. Using integrative analysis, we identified 419 genes highly expressed in spikes, including nine typical homeotic genes of the MADS-box family and the genes TaAP2, TaFL and TaDL. We also identified 143 genes that were significantly different between young spikes of T and D, and 26 genes that were putatively involved in spike differentiation. The result showed that the expression levels of TaAP1-2, TaAP2, and other genes involved in the majority of biological processes such as transcription, translation, cell division, photosynthesis, carbohydrate transport and metabolism, and energy production and conversion were significantly lower in D than in T. Conclusions We identified a set of genes related to wheat floral organ differentiation, including typical homeotic genes. Our results showed that the major causal factors resulting in the spike abnormalities of dms were the lower expression homeotic genes, hormonal imbalance, repressed biological processes, and deficiency of construction materials and energy. We performed a series of studies on the homeotic genes, however the other three causal factors for spike abnormal phenotype of dms need further study. PMID:26982202

  1. Placental programming of chronic diseases, cancer and lifespan: a review.

    Barker, D J P; Thornburg, K L

    2013-10-01

    Particular paths of fetal growth are now known to predict a range of disorders in adult life. This is thought to reflect fetal programming, the phenomenon whereby nutrition and other influences during development set the body's organs and systems for life. The thesis of this review is that normal variations in the processes of placental development lead to variations in the supply of nutrients to the fetus and programme a small number of key systems that are linked to later disease. A baby's growth and nutrition depend both on the function of the placenta, reflected in its gross morphology at birth, and on the mother's lifetime nutrition, reflected in her height and weight. In many studies, the effects of placental size and shape on later disease have been examined within different categories of mother's body size. The review shows that variations in gross placental morphology at birth predict a wide range of disorders in later life. Any particular placental phenotype seems to predict a limited number of diseases. Further research into the links between the processes of placentation and the morphology of the placenta at birth is now required. We need to know more about the relative importance of nutrient flow, nutrient balance and the timing of nutritional events in determining disorders in later life. We also need to understand why, compared to other placental mammals, the human placenta is so variable in its morphology and functional capacity. PMID:23916422

  2. Placental site trophoblastic tumor presented with vaginal metastasis

    Zhang, Hai-Yan; Yue, Xiao-Ni; Tao, Xiang; Xi, Mei-Li; Yan, An-Qi; Lu, Xin

    2015-01-01

    Placental site trophoblastic tumor (PSTT) is a rare type of gestational trophoblastic neoplasia (GTN). It is rising from the abnormal proliferation of intermediate trophoblastic cells with occasional multinuclear giant cells, with the potential for local invasion and metastasis. For its untypical and changeable clinical characteristics, the diagnosis and management are still poorly understood. Here we documented a case of PSTT with vaginal lesion as her unique presentation. After surgery and ...

  3. Placental Transmogrification of the lung

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

    2013-12-15

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

  4. Placental abruption: a persisting killer

    Shakuntala Amirchand Chhabra

    2014-06-01

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

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

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

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

  6. Decorin expression is decreased in first trimester placental tissue from pregnancies with small for gestation age infants at birth.

    Murthi, P; van Zanten, D E; Eijsink, J J H; Borg, A J; Stevenson, J L; Kalionis, B; Chui, A K; Said, J M; Brennecke, S P; Erwich, J J H M

    2016-09-01

    Fetal growth restriction (FGR) is a leading cause of perinatal morbidity and mortality. FGR pregnancies are often associated with histological evidence of placental vascular thrombosis. The proteoglycans are important components and regulators of vascular homeostasis. Previous studies from our laboratory highlighted mRNA and protein expression differences in placental proteoglycan decorin (DCN), within a clinically well-characterised cohort of third-trimester idiopathic FGR compared with gestation-matched uncomplicated control pregnancies. We also showed that decorin contributes to abnormal angiogenesis and increased thrombin generation in vitro. These observations suggest that DCN gene expression may contribute to the etiology of FGR. Small for gestational age (SGA) is frequently used as a proxy for FGR and is defined as a birth weight below the 10th percentile of a birth weight curve. We therefore made use of a unique resource of first trimester tissues obtained via chorionic villus sampling during the first trimester to investigate the temporal relationship between altered DCN expression and any subsequent development of SGA. We hypothesized that placental DCN expression is decreased early in gestation in SGA pregnancies. Surplus chorionic villus specimens from 15 women subsequently diagnosed with FGR and 50 from women with uncomplicated pregnancies were collected. DCN mRNA and DCN protein were determined using real-time PCR and immunoblotting, respectively. Both DCN mRNA and protein were significantly decreased in placentae from first-trimester SGA-pregnancies compared with controls (p development of SGA. PMID:27577711

  7. A clinical case of equine fungal placentitis with reference to hormone profiles and ultrasonography

    MURASE, Harutaka; NIWA, Hidekazu; KATAYAMA, Yoshinari; SATO, Fumio; HADA, Tetsuro; NAMBO, Yasuo

    2016-01-01

    ABSTRACT Fungal placentitis is an infectious disease inducing abortion in pregnant mares. In the present report, we describe a field case of abortion caused by fungal placentitis with consecutive examinations. The progesterone level and combined thickness of the uterus and placenta (CTUP) were abnormal before the onset of clinical signs. Additionally, the estradiol level started to change before the appearance of clinical signs. Abnormal serum amyloid A values and an abnormal fetal heart rate were observed after the onset of clinical signs. The present report demonstrates that the progesterone level and CTUP may be adequate as early diagnostic markers of fungal placentitis and bacterial infection. Endocrinological evaluation based on cutoff values or serial measurements were also useful for early diagnosis. PMID:26858578

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

    Jane Q Chen

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

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

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

    2016-04-01

    Preeclampsia is a pregnancy-specific disorder of new-onset hypertension. Unfortunately, the most effective treatment is early delivery of the fetus and placenta. Placental ischemia appears central to the pathogenesis of preeclampsia because placental ischemia/hypoxia induced in animals by reduced uterine perfusion pressure (RUPP) or in humans stimulates release of hypertensive placental factors into the maternal circulation. The anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1), which antagonizes and reduces bioavailable vascular endothelial growth factor and placental growth factor (PlGF), is elevated in RUPP rats and preeclampsia. Although PlGF and vascular endothelial growth factor are both natural ligands for sFlt-1, vascular endothelial growth factor also has high affinity to VEGFR2 (Flk-1) causing side effects like edema. PlGF is specific for sFlt-1. We tested the hypothesis that PlGF treatment reduces placental ischemia-induced hypertension by antagonizing sFlt-1 without adverse consequences to the mother or fetus. On gestational day 14, rats were randomized to 4 groups: normal pregnant or RUPP±infusion of recombinant human PlGF (180 μg/kg per day; AG31, a purified, recombinant human form of PlGF) for 5 days via intraperitoneal osmotic minipumps. On day 19, mean arterial blood pressure and plasma sFlt-1 were higher and glomerular filtration rate lower in RUPP than normal pregnant rats. Infusion of recombinant human PlGF abolished these changes seen with RUPP along with reducing oxidative stress. These data indicate that the increased sFlt-1 and reduced PlGF resulting from placental ischemia contribute to maternal hypertension. Our novel finding that recombinant human PlGF abolishes placental ischemia-induced hypertension, without major adverse consequences, suggests a strong therapeutic potential for this growth factor in preeclampsia. PMID:26831193

  10. Clustering and classical analysis of clinical and placental phenotypes in fetal growth restriction and constitutional fetal smallness.

    Stanek, Jerzy; Biesiada, Jacek

    2016-06-01

    This study aims to determine whether placental examination can be used to distinguish between pathologic fetal growth restriction (FGR) and constitutional fetal smallness. Data were extracted from a clinicoplacental database of high risk pregnancies during the period 1994-2013. These data were used to compare the 590 consecutive cases having birth weights below the 10th percentile with the 5201 remaining cases having gestational ages ≥20 weeks. The authors analyzed 20 clinical and 46 placental phenotypes using classical statistics, clustering analysis, and multidimensional scaling. Of the low-birth-weight babies, the following types of cases were compared: Four categories of placental phenotypes (those with features of poor uteroplacental perfusion, postuterine placental pathology, chronic inflammation, and a mixed category) better defined the presumably true FGR than did the clinical phenotypes. Maternal smoking and oligohydramnios were associated with fewer abnormal placental phenotypes than were maternal hypertensive diseases and abnormal Dopplers. Early-onset cases of fetal smallness clustered with placental features of poor uteroplacental perfusion, whereas late onset cases did not. Placental examination helps to retrospectively distinguish constitutionally small fetuses from those that are pathologically growth restricted. The latter correlate best with the clinical risk for FGR and with early-onset FGR. This correlation may have prognostic significance for the child and for future pregnancies, since hypoxic placental lesions can occur without clinical risk factors but with a tendency to recur in future pregnancies. PMID:27238719

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

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

    2016-06-01

    Apert and Crouzon are the most common craniosynostosis syndromes associated with mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. We conducted a study to examine the molecular biology, brain abnormalities, and cognitive development of individuals with these syndromes. A retrospective longitudinal review of 14 patients with Apert and Crouzon syndromes seen at the outpatient Craniofacial Surgery Hospital for Rehabilitation of Craniofacial Anomalies in Brazil from January 1999 through August 2010 was performed. Patients between 11 and 36 years of age (mean 18.29 ± 5.80), received cognitive evaluations, cerebral magnetic resonance imaging, and molecular DNA analyses. Eight patients with Apert syndrome (AS) had full scale intelligence quotients (FSIQs) that ranged from 47 to 108 (mean 76.9 ± 20.2), and structural brain abnormalities were identified in five of eight patients. Six patients presented with a gain-of-function mutation (p.Ser252Trp) in FGFR2 and FSIQs in those patients ranged from 47 to78 (mean 67.2 ± 10.7). One patient with a gain-of-function mutation (p.Pro253Arg) had a FSIQ of 108 and another patient with an atypical splice mutation (940-2A →G) had a FSIQ of 104. Six patients with Crouzon syndrome had with mutations in exons IIIa and IIIc of FGFR2 and their FSIQs ranged from 82 to 102 (mean 93.5 ± 6.7). These reveal that molecular aspects are another factor that can be considered in studies of global and cognitive development of patients with Apert and Crouzon syndrome (CS). © 2016 Wiley Periodicals, Inc. PMID:27028366

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

    Lopalco A

    2015-03-01

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

  13. Review: Cell-free fetal DNA in the maternal circulation as an indication of placental health and disease

    Taglauer, E.S.; Wilkins-Haug, L.; Bianchi, D.W.

    2016-01-01

    In human pregnancy, the constant turnover of villous trophoblast results in extrusion of apoptotic material into the maternal circulation. This material includes cell-free (cf) DNA, which is commonly referred to as “fetal”, but is actually derived from the placenta. As the release of cf DNA is closely tied to placental morphogenesis, conditions associated with abnormal placentation, such as preeclampsia, are associated with high DNA levels in the blood of pregnant women. Over the past five years, the development and commercial availability of techniques of massively parallel DNA sequencing have facilitated noninvasive prenatal testing (NIPT) for fetal trisomies 13, 18, and 21. Clinical experience accrued over the past two years has highlighted the importance of the fetal fraction (ff) in cf DNA analysis. The ff is the amount of cell-free fetal DNA in a given sample divided by the total amount of cell-free DNA. At any gestational age, ff has a bell-shaped distribution that peaks between 10 and 20% at 10–21 weeks. ff is affected by maternal body mass index, gestational age, fetal aneuploidy, and whether the gestation is a singleton or multiple. In approximately 0.1% of clinical cases, the NIPT result and a subsequent diagnostic karyotype are discordant; confined placental mosaicism has been increasingly reported as an underlying biologic explanation. Cell-free fetal DNA is a new biomarker that can provide information about the placenta and potentially be used to predict clinical problems. Knowledge gaps still exist with regard to what affects production, metabolism, and clearance of feto-placental DNA. PMID:24388429

  14. Individual grain orientations and texture development of nanocrystalline electrodeposits showing abnormal grain growth

    Klement, Uta [Department of Materials and Manufacturing Technology, Chalmers University of Technology, SE-41296 Gothenburg (Sweden)]. E-mail: uta.klement@chalmers.se; Silva, Melina da [Department of Materials and Manufacturing Technology, Chalmers University of Technology, SE-41296 Gothenburg (Sweden)

    2007-05-31

    The electron backscatter diffraction (EBSD) technique has been used to determine grain orientations of abnormally grown grains in nanocrystalline Ni electrodeposits upon annealing. The results show that the first grown grains have a <3 1 1>//ND orientation. Upon annealing further grain growth occurs and the preferred alignment of the abnormally growing grains changes from <3 1 1>//ND to <1 1 1>//ND. The subgrain coalescence model adopted from recrystallization is used to describe the occurrence of abnormal grain growth, and energy considerations are put forward for explaining the dominance of the <1 1 1>//ND texture component after longer annealing treatments.

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

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

    2016-05-01

    The incidence of maternal obesity and its co-morbidities (diabetes, cardiovascular disease) continues to increase at an alarming rate, with major public health implications. In utero exposure to maternal obesity has been associated with development of cardiovascular and metabolic diseases in the offspring as a result of developmental programming. The placenta regulates maternal-fetal metabolism and shows significant changes in its function with maternal obesity. Autophagy is a cell-survival process, which is responsible for the degradation of damaged organelles and misfolded proteins. Here we show an activation of autophagosomal formation and autophagosome-lysosome fusion in placentas of males but not females from overweight (OW) and obese (OB) women vs. normal weight (NW) women. However, total autophagic activity in these placentas appeared to be decreased as it showed an increase in SQSTM1/p62 and a decrease in lysosomal biogenesis. A mouse model with a targeted deletion of the essential autophagy gene Atg7 in placental tissue showed significant placental abnormalities comparable to those seen in human placenta with maternal obesity. These included a decrease in expression of mitochondrial genes and antioxidants, and decreased lysosomal biogenesis. Strikingly, the knockout mice were developmentally programmed as they showed an increased sensitivity to high-fat diet-induced obesity, hyperglycemia, hyperinsulinemia, increased adiposity, and cardiac remodeling. In summary, our results indicate a sexual dimorphism in placental autophagy in response to maternal obesity. We also show that autophagy plays an important role in placental function and that inhibition of placental autophagy programs the offspring to obesity, and to metabolic and cardiovascular diseases. PMID:26986453

  16. Clinical Anylisis of Placental Abruption in 119 Cases%119例胎盘早剥的临床分析

    余关佳; 李俊男; 王琳; 刘颖蔚; 常青

    2011-01-01

    placental abruption( P<0. 01 ). 6 cases was utedne apoplexy(56. 3% ), 1 case was DIC. Cesarean section had performed in 85 cases, 33 cases were vaginal delivery, and subtotal hysterectomy was performed in one case. Dead fetus was 19 cases. 29 fetus were transferred to lntensive Care Unit. The incidence of newbom and pednatal mortality was zero. Conclusions: From the onset of the initial clinical sign to treatment is associated with the severity of placental abruption. The clinical manifestations of placental abruption are confused with threatened labor, in labor or fetal distress. Missed diagnosis by ultrasound in placenta abruption would occur when the placenta is located on posterior wall or abnormal development of placenta.

  17. The endocannabinoid system: A novel player in human placentation.

    Costa, M A

    2016-06-01

    Cannabis sativa is the most consumed illegal drug around the world. Its consumption during pregnancy is associated with gestational complications, particularly with fetal growth restriction. Endocannabinoids (eCBs) are lipid molecules that act by activating the G-protein coupled cannabinoid receptors, which are also target of the phytocannabinoid Δ(9)-tetrahydrocannabinol (THC). The endocannabinoid system (ECS) participates in distinct biological processes, including pain, inflammation, neuroprotection, and several reproductive events. In addition, an abnormal expression of ECS is associated with infertility and miscarriages. This manuscript will review and discuss the expression of ECS in normal and pathological human placentas, and the role of eCBs and THC in trophoblast proliferation, apoptosis, differentiation, and function. The current evidence points towards a role of ECS in human placentation, shedding light on the contribution of the eCBs in the coordination of human placentation, and in the cellular mechanisms underlying the deleterious effects of cannabis consumption during pregnancy. PMID:26965993

  18. Selenoprotein N deficiency in mice is associated with abnormal lung development.

    Moghadaszadeh, Behzad; Rider, Branden E; Lawlor, Michael W; Childers, Martin K; Grange, Robert W; Gupta, Kushagra; Boukedes, Steve S; Owen, Caroline A; Beggs, Alan H

    2013-04-01

    Mutations in the human SEPN1 gene, encoding selenoprotein N (SepN), cause SEPN1-related myopathy (SEPN1-RM) characterized by muscle weakness, spinal rigidity, and respiratory insufficiency. As with other members of the selenoprotein family, selenoprotein N incorporates selenium in the form of selenocysteine (Sec). Most selenoproteins that have been functionally characterized are involved in oxidation-reduction (redox) reactions, with the Sec residue located at their catalytic site. To model SEPN1-RM, we generated a Sepn1-knockout (Sepn1(-/-)) mouse line. Homozygous Sepn1(-/-) mice are fertile, and their weight and lifespan are comparable to wild-type (WT) animals. Under baseline conditions, the muscle histology of Sepn1(-/-) mice remains normal, but subtle core lesions could be detected in skeletal muscle after inducing oxidative stress. Ryanodine receptor (RyR) calcium release channels showed lower sensitivity to caffeine in SepN deficient myofibers, suggesting a possible role of SepN in RyR regulation. SepN deficiency also leads to abnormal lung development characterized by enlarged alveoli, which is associated with decreased tissue elastance and increased quasi-static compliance of Sepn1(-/-) lungs. This finding raises the possibility that the respiratory syndrome observed in patients with SEPN1 mutations may have a primary pulmonary component in addition to the weakness of respiratory muscles. PMID:23325319

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

    Bernd Rosenbusch

    2012-12-01

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

  20. Normal and abnormal development of mentalization and development of borderline personality disorder as mentalization dysfunction in the context of development of attachment relation

    Adamczyk, Leszek

    2013-01-01

    The aim of this article is to describe the normal and abnormal development of mentallisation and development of borderline personality disorder as a mentallisation dysfunction, in the context of development of attachment relation. Borderline personality disorder is a distinct clinical syndrome with important implications for public health; patients show reduced capacities to mentalise, which inevitably leads to problems in interpersonal relationships, identity disturbance, impulsivity, emotio...

  1. Unsupervised Placental Gene Expression Profiling Identifies Clinically Relevant Subclasses of Human Preeclampsia.

    Leavey, Katherine; Benton, Samantha J; Grynspan, David; Kingdom, John C; Bainbridge, Shannon A; Cox, Brian J

    2016-07-01

    Preeclampsia (PE) is a complex, hypertensive disorder of pregnancy, demonstrating considerable variability in maternal symptoms and fetal outcomes. Unfortunately, prior research has not accounted for this variability, resulting in a lack of robust biomarkers and effective treatments for PE. Here, we created a large (N=330) clinically relevant human placental microarray data set, consisting of 7 previously published studies and 157 highly annotated new samples from a single BioBank. Applying unsupervised clustering to this combined data set identified 3 clinically significant probable etiologies of PE: "maternal", with healthy placentas and term deliveries; "canonical", exhibiting expected clinical, ontological, and histopathologic features of PE; and "immunologic" with severe fetal growth restriction and evidence of maternal antifetal rejection. Moreover, these groups could be distinguished using a small quantitative polymerase chain reaction panel and demonstrated varying influence of maternal factors on PE development. An additional subclass of PE placentas was also revealed to form because of chromosomal abnormalities in these samples, supported by array-based comparative genomic hybridization analysis. Overall, our findings represent a new paradigm in our understanding of the origins and maternal-placental contributions to the pathology of PE. The study of PE represents a unique opportunity to access human tissue associated with a complex hypertensive disorder, and our novel approach could be applied to other hypertensive and heterogeneous human diseases. PMID:27160201

  2. Vitamin D Receptor Gene Ablation in the Conceptus Has Limited Effects on Placental Morphology, Function and Pregnancy Outcome

    Wilson, Rebecca L.; Buckberry, Sam; Spronk, Fleur; Laurence, Jessica A.; Leemaqz, Shalem; O’Leary, Sean; Bianco-Miotto, Tina; Du, Jing; Anderson, Paul H; Roberts, Claire T.

    2015-01-01

    Vitamin D deficiency has been implicated in the pathogenesis of several pregnancy complications attributed to impaired or abnormal placental function, but there are few clues indicating the mechanistic role of vitamin D in their pathogenesis. To further understand the role of vitamin D receptor (VDR)-mediated activity in placental function, we used heterozygous Vdr ablated C57Bl6 mice to assess fetal growth, morphological parameters and global gene expression in Vdr null placentae. Twelve Vdr...

  3. SONOGRAPHIC EVALUATION OF PLACENTAL THICKNESS – AN INDICATOR OF GESTATIONAL AGE

    Anu

    2016-02-01

    Full Text Available AIMS AND OBJECTIVES The purpose of this study was to evaluate the placental thickness by sonography in normal singleton pregnancies at different stages of gestation in order to develop this as a useful tool for gestational age estimation. MATERIALS AND METHODS We evaluated 310 normal singleton pregnancies and calculated the fetal gestational age using sonographic biometric criteria for different periods of gestation. Placental thickness was measured by sonography at the site of umbilical cord insertion using the standardized technique. Mean placental thickness along with its standard deviation and 95 % confidence interval was calculated for each week of gestation. We used correlation regression analysis to study the relationship between placental thickness and gestational age. RESULTS Mean placental thickness (in mm closely matched the gestational age (in weeks between 10 to 30 weeks of gestation. We established a nomogram for placental thickness measurements with increasing gestational age. CONCLUSIONS Placental thickness has a linear relationship with gestational age especially during the second trimester of pregnancy. Placental thickness measurements when used along with fetal biometry can increase the accuracy of predicting gestational age during pregnancy. The regression equation and nomogram developed by us can be used to calculate the gestational age with minimal error.

  4. Placental diversity in malagasy tenrecs

    Enders, A C; Blankenship, T N; Goodman, S M; Soarimalala, V; Carter, Anthony Michael

    2007-01-01

    haemophagous region. In addition, a more villous portion of the placental disk forms before the formation of a more compact labyrinth. Although the definitive placenta is cellular haemomonochorial, it lacks the spongy zone found in the Tenrecinae. Neither does it resemble the endotheliochorial condition found...

  5. Constitutively activated NLRP3 inflammasome causes inflammation and abnormal skeletal development in mice.

    Sheri L Bonar

    Full Text Available The NLRP3 inflammasome complex is responsible for maturation of the pro-inflammatory cytokine, IL-1β. Mutations in NLRP3 are responsible for the cryopyrinopathies, a spectrum of conditions including neonatal-onset multisystem inflammatory disease (NOMID. While excessive production of IL-1β and systemic inflammation are common to all cryopyrinopathy disorders, skeletal abnormalities, prominently in the knees, and low bone mass are unique features of patients with NOMID. To gain insights into the mechanisms underlying skeletal abnormalities in NOMID, we generated knock-in mice globally expressing the D301N NLRP3 mutation (ortholog of D303N in human NLRP3. NOMID mice exhibit neutrophilia in blood and many tissues, including knee joints, and high levels of serum inflammatory mediators. They also exhibit growth retardation and severe postnatal osteopenia stemming at least in part from abnormally accelerated bone resorption, attended by increased osteoclastogenesis. Histologic analysis of knee joints revealed abnormal growth plates, with loss of chondrocytes and growth arrest in the central region of the epiphyses. Most strikingly, a tissue "spike" was observed in the mid-region of the growth plate in the long bones of all NOMID mice that may be the precursor to more severe deformations analogous to those observed in NOMID patients. These findings provide direct evidence linking a NOMID-associated NLRP3-activating mutation to abnormalities of postnatal skeletal growth and bone remodeling.

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

    Takamasa Ishii

    2014-01-01

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

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

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

    2011-01-01

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

  8. MR imaging of the clival bone marrow. Normal development and abnormal findings

    We studied the MR appearance of the normal and abnormal clivus. The bone marrow of the normal clivus in most infants of less than 1 year of age had uniformly low signal intensity relative to the pons (pattern I-1) in T1 weighted images. The proportion of individuals with a I-1 clivus pattern decreased rapidly as a function of age, while that of subjects with marrows of low and high signal intensity (pattern II) and uniformly high signal intensity (pattern III) increased gradually. No marrow with a I-1 pattern was seen after the age of 20. We also investigated the data a available from scout images as it has been shown that this modality may provide clinically significant information. Clival enhancement was observed in only four (5%) of 75 normal subjects. The signal intensity patterns of abnormal clivi could be readily distinguished from those of normal clivi. For example, a uniformly low signal intensity relative to the pons was seen in all 10 patients with tumor invasion investigated by us. Moreover, there was also enhancement in all abnormal clivi. T2-weighted images appeared to be of no value in the characterization of bone marrow disorders. It is concluded from these observations that a clivus of an individual over the age of 20 is considered abnormal when it displays a low signal intensity relative to the pons. (author)

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

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

    2014-03-01

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

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

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

  11. Abnormality of Development in Strongylocentrotus intermedius (A. Agassiz) Larvae from Polluted Habitat in Amursky Bay, Peter the Great Bay

    Naidenko, Tamara

    1997-01-01

    Amursky Bay, Peter the Great Bay, Sea of Japan is very much prone to anthropogenic pollution by heavy metals, oils, phenols, pesticides, etc. To clarify the effect of pollution, tests of the embryonic and larval development of sea urchin Strongylocentrotus intermedius are conducted using material collected from polluted habitats in Amursky Bay. A population from an unpolluted site in Vityaz Bay is used as a control. Various abnormal patterns of development including failure to metamorphose ar...

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

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

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

    Mohanty, April F., E-mail: april.mohanty@va.gov [Cardiovascular Health Research Unit, University of Washington, 1730 Minor Ave, Seattle, WA 98101 (United States); Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA (United States); Farin, Fred M., E-mail: freddy@u.washington.edu [Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, 4225 Roosevelt Way N.E., Suite #100, Seattle, WA 98105 (United States); Bammler, Theo K., E-mail: tbammler@u.washington.edu [Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, 4225 Roosevelt Way N.E., Suite #100, Seattle, WA 98105 (United States); MacDonald, James W., E-mail: jmacdon@uw.edu [Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, 4225 Roosevelt Way N.E., Suite #100, Seattle, WA 98105 (United States); Afsharinejad, Zahra, E-mail: zafshari@u.washington.edu [Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, 4225 Roosevelt Way N.E., Suite #100, Seattle, WA 98105 (United States); Burbacher, Thomas M., E-mail: tmb@uw.edu [Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Box: 357234, 1705 N.E. Pacific Street, Seattle, WA 98195 (United States); Siscovick, David S., E-mail: dsiscovick@nyam.org [Cardiovascular Health Research Unit, University of Washington, 1730 Minor Ave, Seattle, WA 98101 (United States); Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA (United States); Department of Medicine, University of Washington, Seattle, WA (United States); and others

    2015-04-15

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

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

    Hamilton Jill K

    2010-10-01

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

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

    Rodrigo M Souza

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

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

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

  17. Sildenafil attenuates placental ischemia-induced hypertension.

    George, Eric M; Palei, Ana C; Dent, Edward A; Granger, Joey P

    2013-08-15

    Preeclampsia is a complication of pregnancy that is marked by hypertension, proteinuria, and maternal endothelial dysfunction. A central factor in the etiology of the disease is the development of placental hypoxia/ischemia, which releases pathogenic soluble factors. There is currently no effective treatment for preeclampsia, but the phosphodiesterase-5 (PDE-5) inhibitor sildenafil has been suggested, as PDE-5 is enriched in the uterus, and its antagonism could improve uteroplacental function. Here, we report in the reduced uterine perfusion pressure (RUPP) rat model that administration of oral sildenafil is effective in attenuating placental ischemia-induced hypertension during gestation. RUPP animals have significantly elevated arterial pressure compared with control animals (132 ± 3 vs. 100 ± 2 mmHg; P PDE-5/β-actin ratio (1 ± 0.14 vs. 1.63 ± 0.18; P < 0.05) expression with a resulting reduction in renal medullary cGMP (1.5 ± 0.15 vs. 0.99 ± 0.1 pmol/μg protein, P < 0.05) compared with controls. Although sildenafil had no effect on renal medullary cGMP in control animals, it significantly increased cGMP in RUPP animals (1.3 ± 0.1 pmol/μg protein; P < 0.05). These data suggest that sildenafil might provide an effective therapeutic option for the management of hypertension during preeclampsia. PMID:23785075

  18. Megalin–deficiency causes high myopia, retinal pigment epithelium-macromelanosomes and abnormal development of the ciliary body in mice

    Storm, Tina; Heegaard, Steffen; Christensen, Erik I; Nielsen, Rikke

    2014-01-01

    In man, mutations of the megalin-encoding gene causes the rare Donnai-Barrow/Facio-Oculo-Acoustico-Renal Syndrome, which is partially characterized by high-grade myopia. Previous studies of renal megalin function have established that megalin is crucial for conservation of renal filtered nutrients...... megalin localizes to vesicular structures in the RPE and NPCBE cells. Histological investigations of ocular mouse tissue also identified a severe myopia phenotype as well as enlarged RPE melanosomes and abnormal ciliary body development in the megalin-deficient mice. In conclusion, the complex ocular...... phenotype observed in the megalin-deficient mice suggests that megalin-mediated developmental abnormalities may contribute to the high myopia phenotype observed in the Donnai-Barrow Syndrome patients and, thus, that megalin harbors important roles in ocular development and physiology. Finally, our data show...

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

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

    2015-01-01

    of VAR2CSA, a parasite-derived antigen. Protection against PM is mediated by antibodies that inhibit binding of IE in the placental intervillous space. VAR2CSA is a large antigen incompatible with large scale recombinant protein expression. Vaccines based on sub-units encompassing the functionally...... constrained receptor-binding domains may, theoretically, circumvent polymorphisms, reduce the risk of escape-mutants and induce cross-reactive antibodies. However, the sub-unit composition and small differences in the borders, may lead to exposure of novel immuno-dominant antibody epitopes that lead to non......-functional antibodies, and furthermore influence the folding, stability and yield of expression. Candidate antigens from the pre-clinical development expressed in High-Five insect cells using the baculovirus expression vector system were transitioned into the Drosophila Schneider-2 cell (S2) expression-system compliant...

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

    Vinicius S Carreira

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

  1. CORRELATION OF PRENATAL ULTRASOUND FINDINGS WITH PLACENTAL PATHOLOGY IN HIGH RISK PREGNANCY

    Megha

    2014-01-01

    Full Text Available OBJECTIVE: To correlate the prenatal ultrasound findings with placental pathology in high risk pregnancy. METHOD: After approval by institutional ethical committee the prospective observational study was conducted in the department of obstetrics & gynecolo gy , NSCB Medical College , Jabalpur (M.P. from 1st September 201 0 to 31st august 2011. A total of 77 cases were studied including antenatal women with mean gestational age >= 28 weeks not in active labor with high risk factor (inclusion criteria. Prenatal ultrasound and histomorphology of placenta was done in the respective department of the same institution. Statistical analysis was done by using t test and chi square test. RESULT: The sensitivity of prenatal ultrasound to detect retroplacental clot was 1 6.7%.The cases with severe pre - eclampsia and IUGR had more number of cases with abnormal flow in Color Doppler than there with other risk factor. Infarcts and retroplacental clot were found only in cases of severe pre - eclampsia. The sensitivity of color Do ppler to detect abnormal placental pathology was found to be 76% . The prenatal ultrasound was not found sensitive enough to detect the placental infarcts. CONCLUSION: Placental pathologies adversely affect the perinatal outcome. Prenatal USG can identify a range of these abnormalities and can help to take timely action during antenatal period to improve the perinatal outcome

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

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

    2015-01-01

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

  3. Silencing Abnormal Wing Disc Gene of the Asian Citrus Psyllid, Diaphorina citri Disrupts Adult Wing Development and Increases Nymph Mortality

    El-Shesheny, Ibrahim; Hajeri, Subhas; El-Hawary, Ibrahim; Gowda, Siddarame; Killiny, Nabil

    2013-01-01

    Huanglongbing (HLB) causes considerable economic losses to citrus industries worldwide. Its management depends on controlling of the Asian citrus Psyllid (ACP), the vector of the bacterium, Candidatus Liberibacter asiaticus (CLas), the causal agent of HLB. Silencing genes by RNA interference (RNAi) is a promising tool to explore gene functions as well as control pests. In the current study, abnormal wing disc (awd) gene associated with wing development in insects is used to interfere with the...

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

    Nielsen, Morten A; Resende, Mafalda; de Jongh, Willem A; Ditlev, Sisse B; Mordmüller, Benjamin; Houard, Sophie; Ndam, Nicaise Tuikue; Agerbæk, Mette Ø; Hamborg, Mette; Massougbodji, Achille; Issifou, Saddou; Strøbæk, Anette; Poulsen, Lars; Leroy, Odile; Kremsner, Peter G; Chippaux, Jean-Philippe; Luty, Adrian J F; Deloron, Philippe; Theander, Thor G; Dyring, Charlotte; Salanti, Ali

    2015-01-01

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

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

    Morten A Nielsen

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

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

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

    2016-01-01

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

  7. Development of a sintering methodology through abnormal glow discharge for manufacturing metal matrix composites

    Pérez, S.; Pineda, Y.; Sarmiento, A.; López, A.

    2016-02-01

    In this study, a sintering methodology is presented by using abnormal glow discharge to metal matrix composites (MMC), consisting of 316 steel, reinforced with titanium carbide (TiC). The wear behaviour of these compounds was evaluated according to the standard ASTM G 99 in a tribometer pin-on-disk. The effect of the percentage of reinforcement (3, 6, and 9%), with 40 minutes of mixing in the planetary mill is analysed, using compaction pressure of 700MPa and sintering temperature of 1,100°C±5°C, gaseous atmosphere of H2 - N2, and sintering time of 30 minutes. As a result of the research, it shows that the best behaviour against wear is obtained when the MMC contains 6% TiC. Under this parameter the lowest percentage of pores and the lowest coefficient of friction are achieved, ensuring that the incorporation of ceramic particles (TiC) in 316 austenitic steel matrix significantly improves the wear resistance. Also, it is shown that it is possible to sinter such materials using the abnormal glow discharge, being a novel and effective method in which the working temperature is reached in a short time.

  8. Association between calcifying nanoparticles and placental calcification

    Zhang D

    2012-03-01

    Full Text Available Yanan Guo1, Dechun Zhang1, He Lu1, Shuang Luo2, Xuecheng Shen31Molecular Medicine and Tumor Research Center, Chongqing Medical University, Yuzhong District, 2Department of Obstetrics and Gynecology, First Affiliated Hospital of Chongqing Medical University, 3Urological Research Institute of PLA, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of ChinaBackground: The purpose of this study was to examine the possible contribution of calcifying nanoparticles to the pathogenesis of placental calcification.Methods: Calcified placental tissues and distal tissue samples were collected from 36 confirmed placental calcification cases. In addition, 20 normal placental tissue samples were obtained as a control group. All the tissue samples were cultured using special nanobacterial culture methods. The cultured calcifying nanoparticles were examined by transmission electron microscopy (TEM, and their growth was monitored by optical density (OD at a wavelength of 650 nm. 16S rRNA gene expression of the cultured calcifying nanoparticles was also isolated and sequenced.Results: Novel calcifying nanoparticles wrapped with electron-dense shells between 50 nm to 500 nm in diameter were observed in the extracellular matrix of calcified placental tissues. They were detected in placental villi and hydroxyapatite crystals, and contained “nucleic acid-like materials”. After isolation and four weeks of culture, 28 of 36 calcified placental tissue samples showed white granular precipitates attached to the bottom of the culture tubes. OD650 measurements indicated that the precipitates from the calcified placental tissues were able to grow in culture, whereas no such precipitates from the control tissues were observed. The 16S rRNA genes were isolated from the cultured calcifying nanoparticles and calcified placental tissues, and their gene sequencing results implied that calcifying nanoparticles were novel nanobacteria (GenBank JF

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

    Nalliah Sivalingam

    2010-09-01

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

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

    Carlström, Mattias; Wentzel, Parri; Skøtt, Ole; Persson, A Erik G; Eriksson, Ulf J

    2009-01-01

    and fetal outcome exerted by the angiogenesis inhibitor Suramin (100 mg/kg i.p.) during early placentation. Blood pressure and heart rate were measured continuously with telemetry in Sprague-Dawley rats of four experimental groups: nonpregnant controls, Suramin-treated nonpregnant rats, pregnant...... the mesometrial triangle was smaller in the pregnant Suramin-treated rats group than in the pregnant control rats group. CONCLUSION: The inhibition of uterine angiogenesis increases maternal blood pressure and compromises fetal and placental development. Placental hypoxia and subsequent activation of...

  11. Normal and abnormal development of mentalization and development of borderline personality disorder as mentalization dysfunction in the context of development of attachment relation

    Adamczyk, Leszek

    2013-12-01

    Full Text Available The aim of this article is to describe the normal and abnormal development of mentallisation and development of borderline personality disorder as a mentallisation dysfunction, in the context of development of attachment relation. Borderline personality disorder is a distinct clinical syndrome with important implications for public health; patients show reduced capacities to mentalise, which inevitably leads to problems in interpersonal relationships, identity disturbance, impulsivity, emotional regulation and suicidal threats. In this article author present a review of a construct of mentallisation as it is developed by P. Fonagy and his collaborators. Mentalising is the process of making sense of mental states in oneself and other persons in terms of subjective states and mental processes. The concept of mentallisation is rooted in attachment theory. The author reviews the biobehavioural switch–model of the relationship between attachment, arousal or stress, mentallisation, and development of borderline personality disorder.

  12. Microparasites and Placental Invasiveness in Eutherian Mammals.

    Isabella Capellini

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

  13. Placentation in different mammalian species.

    Chavatte-Palmer, Pascale; Tarrade, Anne

    2016-06-01

    The placenta is a complex, transient organ associated with viviparity, which is located at the interface of the dam and fetus during pregnancy. It is formed after attachment, or implantation, of the blastocyst on the uterine lining and derives from complex cellular and molecular interactions between uterine and embryonic tissues. In mammals, there are many forms of placentation but this organ has the same function in all species: it is responsible for orchestrating materno-fetal exchanges, together with endocrine and immunological functions. PMID:27155775

  14. Sirh7/Ldoc1 knockout mice exhibit placental P4 overproduction and delayed parturition.

    Naruse, Mie; Ono, Ryuichi; Irie, Masahito; Nakamura, Kenji; Furuse, Tamio; Hino, Toshiaki; Oda, Kanako; Kashimura, Misho; Yamada, Ikuko; Wakana, Shigeharu; Yokoyama, Minesuke; Ishino, Fumitoshi; Kaneko-Ishino, Tomoko

    2014-12-01

    Sirh7/Ldoc1 [sushi-ichi retrotransposon homolog 7/leucine zipper, downregulated in cancer 1, also called mammalian retrotransposon-derived 7 (Mart7)] is one of the newly acquired genes from LTR retrotransposons in eutherian mammals. Interestingly, Sirh7/Ldoc1 knockout (KO) mice exhibited abnormal placental cell differentiation/maturation, leading to an overproduction of placental progesterone (P4) and placental lactogen 1 (PL1) from trophoblast giant cells (TGCs). The placenta is an organ that is essential for mammalian viviparity and plays a major endocrinological role during pregnancy in addition to providing nutrients and oxygen to the fetus. P4 is an essential hormone in the preparation and maintenance of pregnancy and the determination of the timing of parturition in mammals; however, the biological significance of placental P4 in rodents is not properly recognized. Here, we demonstrate that mouse placentas do produce P4 in mid-gestation, coincident with a temporal reduction in ovarian P4, suggesting that it plays a role in the protection of the conceptuses specifically in this period. Pregnant Sirh7/Ldoc1 knockout females also displayed delayed parturition associated with a low pup weaning rate. All these results suggest that Sirh7/Ldoc1 has undergone positive selection during eutherian evolution as a eutherian-specific acquired gene because it impacts reproductive fitness via the regulation of placental endocrine function. PMID:25468940

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

    Nielsen, Morten A.; Mafalda Resende; de Jongh, Willem A.; Ditlev, Sisse B.; Benjamin Mordmüller; Sophie Houard; Nicaise Tuikue Ndam; Mette Ø Agerbæk; Mette Hamborg; Achille Massougbodji; Saddou Issifou; Anette Strøbæk; Lars Poulsen; Odile Leroy; Kremsner, Peter G

    2015-01-01

    The disease caused by Plasmodium falciparum (Pf) involves different clinical manifestations that, cumulatively, kill hundreds of thousands every year. Placental malaria (PM) is one such manifestation in which Pf infected erythrocytes (IE) bind to chondroitin sulphate A (CSA) through expression of VAR2CSA, a parasite-derived antigen. Protection against PM is mediated by antibodies that inhibit binding of IE in the placental intervillous space. VAR2CSA is a large antigen incompatible with large...

  16. Nomenclature and placental mammal phylogeny

    Helgen Kristofer M

    2010-04-01

    Full Text Available Abstract An issue arising from recent progress in establishing the placental mammal Tree of Life concerns the nomenclature of high-level clades. Fortunately, there are now several well-supported clades among extant mammals that require unambiguous, stable names. Although the International Code of Zoological Nomenclature does not apply above the Linnean rank of family, and while consensus on the adoption of competing systems of nomenclature does not yet exist, there is a clear, historical basis upon which to arbitrate among competing names for high-level mammalian clades. Here, we recommend application of the principles of priority and stability, as laid down by G.G. Simpson in 1945, to discriminate among proposed names for high-level taxa. We apply these principles to specific cases among placental mammals with broad relevance for taxonomy, and close with particular emphasis on the Afrotherian family Tenrecidae. We conclude that no matter how reconstructions of the Tree of Life change in years to come, systematists should apply new names reluctantly, deferring to those already published and maximizing consistency with existing nomenclature.

  17. Placental Responses to Changes in the Maternal Environment Determine Fetal Growth

    Dimasuay, Kris Genelyn; Boeuf, Philippe; Powell, Theresa L.; Jansson, Thomas

    2016-01-01

    Placental responses to maternal perturbations are complex and remain poorly understood. Altered maternal environment during pregnancy such as hypoxia, stress, obesity, diabetes, toxins, altered nutrition, inflammation, and reduced utero-placental blood flow may influence fetal development, which can predispose to diseases later in life. The placenta being a metabolically active tissue responds to these perturbations by regulating the fetal supply of nutrients and oxygen and secretion of hormo...

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

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

    2014-01-01

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

  19. RAT PLACENTATION: AN EXPERIMENTAL MODEL FOR INVESTIGATING THE HEMOCHORIAL MATERNAL-FETAL INTERFACE

    Soares, Michael J.; Chakraborty, Damayanti; Rumi, M. A. Karim; Konno, Toshihiro; Renaud, Stephen J.

    2012-01-01

    The rat possesses hemochorial placentation with deep intrauterine trophoblast cell invasion and trophoblast-directed uterine spiral artery remodeling; features shared with human placentation. Recognition of these similarities spurred the establishment of in vitro and in vivo research methods using the rat as an animal model to address mechanistic questions regarding development of the hemochorial placenta. The purpose of this review is to provide the requisite background to help move the rat ...

  20. The influence of maternal attachment and postpartum depression on abnormal development of the child until the age of 18 months

    Andrea Beetz

    2013-12-01

    Full Text Available Problems in the psychological or physical development of children seem to increase in Western Societies, probably also due to suboptimal interactions with caregivers and insecure attachments, and can be observed already in early childhood. In the present study, the association of children’s abnormal development until the age of 18 months with attachment representation, prenatal attachment and postpartum depression of their 161 primiparae mothers with a relatively high educational background were investigated. A high level of maternal attachment disorganization and even medium levels of postpartum depression were significantly linked to noticeable problems with physical and behavioral development in the regular child screening exams (at 6 and 12 months and with the problem behaviour reported by the mothers. This suggests that also mothers without obvious and known risk factors, who are usually not targeted by early interventions, would profit from professional support. A simple indicator for a screening would be maternal depression at 6 months postpartum.

  1. A panel of free fatty acid ratios to predict the development of metabolic abnormalities in healthy obese individuals.

    Zhao, Linjing; Ni, Yan; Ma, Xiaojing; Zhao, Aihua; Bao, Yuqian; Liu, Jiajian; Chen, Tianlu; Xie, Guoxiang; Panee, Jun; Su, Mingming; Yu, Herbert; Wang, Congrong; Hu, Cheng; Jia, Weiping; Jia, Wei

    2016-01-01

    Increasing evidences support that metabolically healthy obese (MHO) is a transient state. However, little is known about the early markers associated with the development of metabolic abnormalities in MHO individuals. Serum free fatty acids (FFAs) profile is highlighted in its association with obesity-related insulin resistance, type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD). To examine the association of endogenous fatty acid metabolism with future development of metabolic abnormalities in MHO individuals, we retrospectively analyzed 24 [product FFA]/[precursor FFA] ratios in fasting sera and clinical data from 481 individuals who participated in three independent studies, including 131 metabolic healthy subjects who completed the 10-year longitudinal Shanghai Diabetes Study (SHDS), 312 subjects cross-sectionally sampled from the Shanghai Obesity Study (SHOS), and 38 subjects who completed an 8-week very low carbohydrate diet (VLCD) intervention study. Results showed that higher baseline level of oleic acid/stearic acid (OA/SA), and lower levels of stearic acid/palmitic acid (SA/PA) and arachidonic acid/dihomo-γ-linolenic acid (AA/DGLA) ratios were associated with higher rate of MHO to MUO conversion in the longitudinal SHDS. Further, the finding was validated in the cross-sectional and interventional studies. This panel of FFA ratios could be used for identification and early intervention of at-risk obese individuals. PMID:27344992

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

    Prouillac, Caroline, E-mail: c.prouillac@vetagro-sup.fr [Université Lyon, US/C 1233 INRA VetAgroSup, Métabolisme et Toxicologie Comparée des Xénobiotiques, 1 avenue Bourgelat, BP 83, 69280 Marcy l' Etoile (France); Koraichi, Farah; Videmann, Bernadette; Mazallon, Michelle [Université Lyon, US/C 1233 INRA VetAgroSup, Métabolisme et Toxicologie Comparée des Xénobiotiques, 1 avenue Bourgelat, BP 83, 69280 Marcy l' Etoile (France); Rodriguez, Frédéric; Baltas, Michel [Université Paul Sabatier, SPCMIB-UMR5068, Laboratoire de Synthèse et de Physicochimie des Molécules d' Intérêt Biologique, 118 route de Narbonne, 31062 TOULOUSE cedex 9 (France); Lecoeur, Sylvaine [Université Lyon, US/C 1233 INRA VetAgroSup, Métabolisme et Toxicologie Comparée des Xénobiotiques, 1 avenue Bourgelat, BP 83, 69280 Marcy l' Etoile (France)

    2012-03-15

    Zearalenone (ZEN) is a non-steroid estrogen mycotoxin produced by numerous strains of Fusarium which commonly contaminate cereals. After oral administration, ZEN is reduced via intestinal and hepatic metabolism to α- and β-zearalenol (αZEL and βZEL). These reduced metabolites possess estrogenic properties, αZEL showing the highest affinity for ERs. ZEN and reduced metabolites cause hormonal effects in animals, such as abnormalities in the development of the reproductive tract and mammary gland in female offspring, suggesting a fetal exposure to these contaminants. In our previous work, we have suggested the potential impact of ZEN on placental cells considering this organ as a potential target of xenobiotics. In this work, we first compared the in vitro effects of αZEL and βΖΕL on cell differentiation to their parental molecule on human trophoblast (BeWo cells). Secondly, we investigated their molecular mechanisms of action by investigating the expression of main differentiation biomarkers and the implication of nuclear receptor by docking prediction. Conversely to ZEN, reduced metabolites did not induce trophoblast differentiation. They also induced significant changes in ABC transporter expression by potential interaction with nuclear receptors (LXR, PXR, PR) that could modify the transport function of placental cells. Finally, the mechanism of ZEN differentiation induction seemed not to involve nuclear receptor commonly involved in the differentiation process (PPARγ). Our results demonstrated that in spite of structure similarities between ZEN, αZEL and βZEL, toxicological effects and toxicity mechanisms were significantly different for the three molecules. -- Highlights: ► ZEN and metabolites have differential effect on trophoblast differentiation. ► ZEN and metabolites have differential effect on ABC transporter expression. ► ZEN and metabolites effects involved nuclear receptors interaction.

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

    Zearalenone (ZEN) is a non-steroid estrogen mycotoxin produced by numerous strains of Fusarium which commonly contaminate cereals. After oral administration, ZEN is reduced via intestinal and hepatic metabolism to α- and β-zearalenol (αZEL and βZEL). These reduced metabolites possess estrogenic properties, αZEL showing the highest affinity for ERs. ZEN and reduced metabolites cause hormonal effects in animals, such as abnormalities in the development of the reproductive tract and mammary gland in female offspring, suggesting a fetal exposure to these contaminants. In our previous work, we have suggested the potential impact of ZEN on placental cells considering this organ as a potential target of xenobiotics. In this work, we first compared the in vitro effects of αZEL and βΖΕL on cell differentiation to their parental molecule on human trophoblast (BeWo cells). Secondly, we investigated their molecular mechanisms of action by investigating the expression of main differentiation biomarkers and the implication of nuclear receptor by docking prediction. Conversely to ZEN, reduced metabolites did not induce trophoblast differentiation. They also induced significant changes in ABC transporter expression by potential interaction with nuclear receptors (LXR, PXR, PR) that could modify the transport function of placental cells. Finally, the mechanism of ZEN differentiation induction seemed not to involve nuclear receptor commonly involved in the differentiation process (PPARγ). Our results demonstrated that in spite of structure similarities between ZEN, αZEL and βZEL, toxicological effects and toxicity mechanisms were significantly different for the three molecules. -- Highlights: ► ZEN and metabolites have differential effect on trophoblast differentiation. ► ZEN and metabolites have differential effect on ABC transporter expression. ► ZEN and metabolites effects involved nuclear receptors interaction.

  4. Congenital Abnormalities

    ... blood flow to the fetus impair fetal growth. Alcohol consumption and certain drugs during pregnancy significantly increase the risk that a baby will be born with abnormalities (e.g. fetal alcohol spectrum disorders ). Eating raw or uncooked foods during pregnancy can also be dangerous to health of the ...

  5. Placental Microbiome and Its Role in Preterm Birth

    CAO, BIN; Stout, Molly J.; Lee, Iris; Mysorekar, Indira U.

    2014-01-01

    Despite the well-known fact that the placenta has long-term effects on maternal and fetal health, the placenta remains a poorly understood and understudied organ. Not only is the placenta a site of exchange of nutrients and blood and gases between the fetal and maternal systems, but it also performs critical metabolic functions for supporting fetal development and maintaining maternal-fetal tolerance. It is also abundantly clear that impairment of placental function leads to severe pregnancy ...

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

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

  7. The sequential development of abnormal prion protein accumulation in mice with Creutzfeldt-Jakob disease.

    Muramoto, T; Kitamoto, T.; Tateishi, J.; Goto, I.

    1992-01-01

    The distribution and sequential development of prion protein (PrP) accumulation in the central nervous system (CNS) and non-neuronal organs of mice infected with Creutzfeldt-Jakob disease (CJD) were investigated immunohistochemically using a new pretreatment method that greatly enhanced the immunoreactivity of PrP. Prion protein accumulation in the CNS was first detected at 30 days after inoculation and then developed near the inoculation site or periventricular area, and later spread to the ...

  8. The radioimmunoassay of human placental protein 14 (PP14)

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

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

    Kris Genelyn eDimasuay

    2016-01-01

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

  10. Fetal Placental Thrombosis and Neonatal Implications

    Wintermark, Pia; Boyd, Theonia; Parast, Mana M; Van Marter, Linda J; Warfield, Simon K.; Robertson, Richard L.; Ringer, Steven A.

    2009-01-01

    We present the neonatal complications of two premature newborn infants whose placentas demonstrated placental thrombosis in the fetal circulation. Both mothers presented with a 3-day history of decreased fetal movements before delivery. The first infant presented with thrombocytopenia and disseminated intravascular coagulation. The second infant had extended bilateral extended hemorrhagic venous infarctions. Severe fetal placental vascular lesions seem to be a predisposing factor for some adv...

  11. Protein Profiling of Preeclampsia Placental Tissues

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

    2014-01-01

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

  12. Placental pathology: a systematic approach with clinical correlations.

    Redline, R W

    2008-03-01

    Despite advances over the past 25 years in the monitoring of in utero fetal status, the gravid uterus remains a "black box" integrating underlying genetic risk factors, preexisting maternal disease, and injurious extrinsic events in a poorly understood way to produce an evolving state linked to pregnancy outcome. It is currently believed that many short- and long-term adverse pregnancy outcomes and even some long-term chronic diseases extending into adult life are at least in part determined by processes occurring during intrauterine life. The placenta has been described as a "diary of intrauterine life" and has the potential to illuminate many aspects of these processes. Unfortunately a systematic and objective catalog of placental abnormalities has never been agreed upon. This report outlines a simple conceptual framework separating placental patterns of injury and maladaptation into three categories of lesions affecting the maternal and fetal vasculature (maldevelopment, obstruction, and disruption) and two categories of inflammatory lesions (infectious and idiopathic). Data are presented supporting the importance of these processes for an understanding of preterm delivery, intrauterine growth restriction, hypoxic-ischemic injury, and recurrent pregnancy loss. PMID:17950457

  13. DLX4 is associated with orofacial clefting and abnormal jaw development

    Wu, D.; Mandal, S.; Choi, A.; Anderson, A.; Procházková, Michaela; Perry, H.; Gil-Da-Silva-Lopes, V.L.; Lao, R.; Wan, E.; Tang, P.L.F.; Kwok, P.Y.; Klein, O.; Zhuan, B.; Slavotinek, A.M.

    2015-01-01

    Roč. 24, č. 15 (2015), s. 4340-4352. ISSN 0964-6906 Institutional support: RVO:68378050 Keywords : Distal-less 4 gene * craniofacial development * cleft lip and/or palate Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.393, year: 2014

  14. Abnormal coronary tree development in embryonic hypoxia leads to heart failure and embryonic lethality.

    Naňka, O.; Sedmera, David; Grim, M.

    2007-01-01

    Roč. 21, č. 6 (2007), s. 778.8. ISSN 0892-6638. [Experimental Biology 2007. 27.04.2007-03.05.2007, Washington DC] Institutional research plan: CEZ:AV0Z50450515 Keywords : coronary tree development Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  15. Abnormal development of glomerular endothelial and mesangial cells in mice with targeted disruption of the lama3 gene.

    Abrass, C K; Berfield, A K; Ryan, M C; Carter, W G; Hansen, K M

    2006-09-01

    Mice with targeted disruption of the lama3 gene, which encodes the alpha3 chain of laminin-5 (alpha3beta3gamma2, 332), develop a blistering skin disease similar to junctional epidermolysis bullosa in humans. These animals also develop abnormalities in glomerulogenesis. In both wild-type and mutant animals (lama3(-/-)), podocytes secrete glomerular basement membrane and develop foot processes. Endothelial cells migrate into this scaffolding and secrete a layer of basement membrane that fuses with the one formed by the podocyte. In lama3(-/-) animals, glomerular maturation arrests at this stage. Endothelial cells do not attenuate, develop fenestrae, or form typical lumens, and mesangial cells (MCs) were not identified. LN alpha3 subunit (LAMA3) protein was identified in the basement membrane adjacent to glomerular endothelial cells (GEnCs) in normal rats and mice. In developing rat glomeruli, the LAMA3 subunit was first detectable in the early capillary loop stage, which corresponds to the stage at which maturation arrest was observed in the mutant mice. Lama3 mRNA and protein were identified in isolated rat and mouse glomeruli and cultured rat GEnCs, but not MC. These data document expression of LAMA3 in glomeruli and support a critical role for it in GEnC differentiation. Furthermore, LAMA3 chain expression and/or another product of endothelial cells are required for MC migration into the developing glomerulus. PMID:16850021

  16. ABNORMALITIES IN CHILDREN MOTOR DEVELOPMENT AS EARLY SYMPTOMS OF PSYCHOMOTOR DISORDERS

    Nowak, Agata; Romanowska-tolloczko, Anna; Bartusiak, Irena

    2009-01-01

    A child feels, thinks, acts and expresses him/her self while in movement. Movements often reflect emotions, therefore observations and analysis of a child's motor behaviour may be a source of information for an investigator on the mental state, possible behaviour or developmental problems a child might have. This is why the verification of the level of child's development should be more complex than merely based on subjective opinions of teachers or parents. One of the method of assessment of...

  17. Abnormal sympathetic nervous system development and physiologic dysautonomia in Egr3-deficient mice

    Eldredge, Laurie C.; Gao, Xiaoguang M.; Quach, David; LI, Lin; Han, Xiaoqiang; Lomasney, Jon; Tourtellotte, Warren G.

    2008-01-01

    Sympathetic nervous system development depends upon many factors that mediate neuron migration, differentiation and survival. Target tissue-derived nerve growth factor (NGF) signaling-induced gene expression is required for survival, differentiation and target tissue innervation of post-migratory sympathetic neurons. However, the transcriptional regulatory mechanisms mediated by NGF signaling are very poorly defined. Here, we identify Egr3, a member of the early growth response (Egr) family o...

  18. Hippocampal neuronal subtypes develop abnormal dendritic arbors in the presence of Fragile X astrocytes.

    Jacobs, S; Cheng, C; Doering, L C

    2016-06-01

    Astrocytes are now recognized as key players in the neurobiology of neurodevelopmental disorders such as Fragile X syndrome. However, the nature of Fragile X astrocyte-mediated control of dendrite development in subtypes of hippocampal neurons is not yet known. We used a co-culture procedure in which wildtype primary hippocampal neurons were cultured with astrocytes from either a wildtype or Fragile X mouse, for either 7, 14 or 21days. The neurons were processed for immunocytochemistry with the dendritic marker MAP2, classified by morphological criteria into one of five neuronal subtypes, and subjected to Sholl analyses. Both linear and semi-log methods of Sholl analyses were applied to the neurons in order to provide an in depth analysis of the dendritic arborizations. We found that Fragile X astrocytes affect the development of dendritic arborization of all subtypes of wildtype hippocampal neurons. Furthermore, we show that hippocampal neurons with spiny stellate neuron morphology exhibit the most pervasive developmental delays, with significant dendritic arbor alterations persisting at 21days in culture. The results further dictate the critical role astrocytes play in governing neuronal morphology including altered dendrite development in Fragile X. PMID:26968765

  19. Neonatal Lethality, Dwarfism, and Abnormal Brain Development in Dmbx1 Mutant Mice

    Ohtoshi, Akihira; Behringer, Richard R.

    2004-01-01

    Dmbx1 encodes a paired-like homeodomain protein that is expressed in developing neural tissues during mouse embryogenesis. To elucidate the in vivo role of Dmbx1, we generated two Dmbx1 mutant alleles. Dmbx1− lacks the homeobox and Dmbx1z is an insertion of a lacZ reporter gene. Dmbx1z appears to be a faithful reporter of Dmbx1 expression during embryogenesis and after birth. Dmbx1-lacZ expression was detected in the superior colliculus, cerebellar nuclei, and subpopulations of the medulla ob...

  20. Development of a database system for shutdown and abnormal events of nuclear power plants in Korea

    To perform accident analysis (including probabilistic safety analysis) or performance analysis that are requisite for the design of nuclear power plants, events both that have taken place and that have a possibility to be realized have to be classified based on initiating frequencies of them. Up to now, event initiating frequency data obtained from operating experience of foreign countries (especially for U.S.) have been used because the amount of domestic operating experience data are very small. However it is indispensable to collect/analysis domestic operating experience data because these initiating frequencies obtained from operating experience of foreign countries may be different obtained from domestic operating experience. Therefore, not only to manage collected domestic operating experience data efficiently but also to retrieve valuable information including initiating frequencies of events, KTRIP program has been developed in cooperation with KAERI (Korea Atomic Energy Research Institute) and KOPEC (Korea Electric Power Company)

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

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

    2016-05-01

    Triazole fungicides are one of the top ten classes of current-use pesticides. Although exposure to triazole fungicides is associated with reproductive toxicity in mammals, limited information is available regarding the effects of triazole fungicides on human placental trophoblast function. Tebuconazole (TEB) is a common triazole fungicide that has been extensively used for fungi control. In this work, we showed that TEB could reduce cell viability, disturb normal cell cycle distribution and induce apoptosis of human placental trophoblast cell line HTR-8/SVneo (HTR-8). Bcl-2 protein expression decreased and the level of Bax protein increased after TEB treatment in HTR-8 cells. The results demonstrated that this fungicide induced apoptosis of trophoblast cells via mitochondrial pathway. Importantly, we found that the invasive and migratory capacities of HTR-8 cells decreased significantly after TEB administration. TEB altered the expression of key regulatory genes involved in the modulation of trophoblast functions. Taken together, TEB suppressed human trophoblast invasion and migration through affecting the expression of protease, hormones, angiogenic factors, growth factors and cytokines. As the invasive and migratory abilities of trophoblast are essential for successful placentation and fetus development, our findings suggest a potential risk of triazole fungicides to human pregnancy. PMID:26852204

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

    F. Homo-Delarche

    2001-04-01

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

  3. Novel use of proton magnetic resonance spectroscopy (1HMRS to non-invasively assess placental metabolism.

    Fiona C Denison

    Full Text Available BACKGROUND: Placental insufficiency is a major cause of antepartum stillbirth and fetal growth restriction (FGR. In affected pregnancies, delivery is expedited when the risks of ongoing pregnancy outweigh those of prematurity. Current tests are unable to assess placental function and determine optimal timing for delivery. An accurate, non-invasive test that clearly defines the failing placenta would address a major unmet clinical need. Proton magnetic resonance spectroscopy ((1H MRS can be used to assess the metabolic profile of tissue in-vivo. In FGR pregnancies, a reduction in N-acetylaspartate (NAA/choline ratio and detection of lactate methyl are emerging as biomarkers of impaired neuronal metabolism and fetal hypoxia, respectively. However, fetal brain hypoxia is a late and sometimes fatal event in placental compromise, limiting clinical utility of brain (1H MRS to prevent stillbirth. We hypothesised that abnormal placental (1H MRS may be an earlier biomarker of intrauterine hypoxia, affording the opportunity to optimise timing of delivery in at-risk fetuses. METHODS AND FINDINGS: We recruited three women with severe placental insufficiency/FGR and three matched controls. Using a 3T MR system and a combination of phased-array coils, a 20×20×40 mm(1H MRS voxel was selected along the 'long-axis' of the placenta with saturation bands placed around the voxel to prevent contaminant signals. A significant choline peak (choline/lipid ratio 1.35-1.79 was detected in all healthy placentae. In contrast, in pregnancies complicated by FGR, the choline/lipid ratio was ≤0.02 in all placentae, despite preservation of the lipid peak (p<0.001. CONCLUSIONS: This novel proof-of-concept study suggests that in severe placental insufficiency/FGR, the observed 60-fold reduction in the choline/lipid ratio by (1H MRS may represent an early biomarker of critical placental insufficiency. Further studies will determine performance of this test and the potential

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

    Dora Baczyk

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

  5. Maternal soluble fms-like tyrosine kinase-1, placental growth factor, plasminogen activator inhibitor-2, and folate concentrations and early fetal size : the Generation R study

    Bouwland-Both, Marieke I.; Steegers, Eric A. P.; Lindemans, Jan; Russcher, Henk; Hofman, Albert; Geurts-Moespot, Anneke J.; Sweep, Fred C. G. J.; Jaddoe, Vincent W. V.; Steegers-Theunissen, Regine P. M.

    2013-01-01

    OBJECTIVE: Fetal growth is dependent on adequate development of the placenta. Impaired angiogenesis and vasculogenesis in early pregnancy compromises placental and embryonic development. The proteins soluble fms-like tyrosine kinase (sFlt)-1, placental growth factor (PlGF), and plasminogen activator

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

    Ibrahim El-Shesheny

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

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

    Koo, Hyun-Na; Yun, Seung-Hwan; Yoon, Changmann; Kim, Gil-Hah

    2012-01-01

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

  8. ASSOCIATION OF PLACENTAL MORPHOMETRY WITH NEWBORN ANTHROPOMETRY

    Rupa L

    2015-07-01

    Full Text Available BACKGROUND : The fetal growth is the outcome of the maternal nutrient stores and efficient transport across the placenta. Hence, any variation in the placenta leads to disproportionate fetal growth leading to long term risk of chronic diseases in the newborn. This stud y was designed to explore influence of placental morphometry on newborn anthropometry . MATERIALS AND METHOD S : The study was conducted on 391 placentae of singleton newborn from a teaching hospital of North Karnataka, India. Data was collected from August 2 012 to January 2013 by using standard operating procedures in a pre - designed and pre - tested proforma. The distributions of placental morphology and newborn anthropometry are mentioned with their percentiles and Box plots. Analysis of variance is used to st udy the differences in means of placental morphometry in different groups of newborn anthropometry. RESULTS : The Means and standard deviations of placental morphometry; weight, volume, surface area and thickness were 440±100gm, 386±101 ml, 230±50 cm sq , an d 2.1±0.4cm respectively. Mean and standard deviations of birth weight and newborn length were 2700±500 gm. 46.6±2.5cm. Placental morphometry and newborn anthropometry increased significantly with gestation. CONCLUSIONS : This study infers that suboptimal g rowth of placenta leads to adverse pregnancy outcome.

  9. Microcystin-LR induces abnormal root development by altering microtubule organization in tissue-cultured common reed (Phragmites australis) plantlets.

    Máthé, Csaba; Beyer, Dániel; Erdodi, Ferenc; Serfozo, Zoltán; Székvölgyi, Lóránt; Vasas, Gábor; M-Hamvas, Márta; Jámbrik, Katalin; Gonda, Sándor; Kiss, Andrea; Szigeti, Zsuzsa M; Surányi, Gyula

    2009-05-01

    Microcystin-LR (MC-LR) is a heptapeptide cyanotoxin, known to be a potent inhibitor of type 1 and 2A protein phosphatases in eukaryotes. Our aim was to investigate the effect of MC-LR on the organization of microtubules and mitotic chromatin in relation to its possible effects on cell and whole organ morphology in roots of common reed (Phragmites australis). P. australis is a widespread freshwater and brackish water aquatic macrophyte, frequently exposed to phytotoxins in eutrophic waters. Reed plantlets regenerated from embryogenic calli were treated with 0.001-40 microg ml(-1) (0.001-40.2 microM) MC-LR for 2-20 days. At 0.5 microg ml(-1) MC-LR and at higher cyanotoxin concentrations, the inhibition of protein phosphatase activity by MC-LR induced alterations in reed root growth and morphology, including abnormal lateral root development and the radial swelling of cells in the elongation zone of primary and lateral roots. Both short-term (2-5 days) and long-term (10-20 days) of cyanotoxin treatment induced microtubule disruption in meristems and in the elongation and differentiation zones. Microtubule disruption was accompanied by root cell shape alteration. At concentrations of 0.5-5 microg ml(-1), MC-LR increased mitotic index at long-term exposure and induced the increase of the percentage of meristematic cells in prophase as well as telophase and cytokinesis of late mitosis. High cyanotoxin concentrations (10-40 microg ml(-1)) inhibited mitosis at as short as 2 days of exposure. The alteration of microtubule organization was observed in mitotic cells at all exposure periods studied, at cyanotoxin concentrations of 0.5-40 microg ml(-1). MC-LR induced spindle anomalies at the metaphase-anaphase transition, the formation of asymmetric anaphase spindles and abnormal sister chromatid separation. This paper reports for the first time that MC-LR induces cytoskeletal changes that lead to alterations of root architecture and development in common reed and generally, in

  10. Characterization of the Placental Macrophage Secretome: Implications for Antiviral Activity

    García, K.; García, V.; Laspiur, J.Pérez; F. Duan; Meléndez, L.M.

    2008-01-01

    It is well documented that placental macrophages show lower levels of HIV-1 infection than monocyte-derived macrophages (MDM). We used proteomic methods to test the hypothesis that placental macrophages secrete different proteins as compared to MDM that may contribute to decreased HIV-1 replication. Placental macrophages and MDM were cultured for 12 days and supernatant was collected. To characterize supernatants, the protein profiles of placental macrophages and MDM were compared using the p...

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

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

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

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

    2012-01-15

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

  13. Zika Virus Infects Human Placental Macrophages.

    Quicke, Kendra M; Bowen, James R; Johnson, Erica L; McDonald, Circe E; Ma, Huailiang; O'Neal, Justin T; Rajakumar, Augustine; Wrammert, Jens; Rimawi, Bassam H; Pulendran, Bali; Schinazi, Raymond F; Chakraborty, Rana; Suthar, Mehul S

    2016-07-13

    The recent Zika virus (ZIKV) outbreak in Brazil has been directly linked to increased cases of microcephaly in newborns. Current evidence indicates that ZIKV is transmitted vertically from mother to fetus. However, the mechanism of intrauterine transmission and the cell types involved remain unknown. We demonstrate that the contemporary ZIKV strain PRVABC59 (PR 2015) infects and replicates in primary human placental macrophages, called Hofbauer cells, and to a lesser extent in cytotrophoblasts, isolated from villous tissue of full-term placentae. Viral replication coincides with induction of type I interferon (IFN), pro-inflammatory cytokines, and antiviral gene expression, but with minimal cell death. Our results suggest a mechanism for intrauterine transmission in which ZIKV gains access to the fetal compartment by directly infecting placental cells and disrupting the placental barrier. PMID:27247001

  14. Evolution of placental function in mammals

    Carter, Anthony Michael

    2012-01-01

    gas exchange. They evolved following duplications within the beta-globin gene family with convergent evolution occurring in ruminants and primates. In primates there was also an interesting rearrangement of a cassette of genes in relation to an upstream locus control region. Substrate transfer from...... placental lactogens from the growth hormone and prolactin genes. There has been a remarkable degree of convergent evolution with placental lactogens emerging separately in the ruminant, rodent, and primate lineages and chorionic gonadotropins evolving separately in equids and higher primates. Finally......, coevolution in the primate lineage of killer immunoglobulin-like receptors and human leukocyte antigens can be linked to the deep invasion of the uterus by trophoblast that is a characteristic feature of human placentation....

  15. [Antenatal diagnosis of placental acretism-percretism].

    Haghenbeck-Altamirano, Francisco Javier; Leis-Márquez, Teresa; Ayala-Yáñez, Rodrigo; Juárez-García, Luz del Carmen; García-Moreno, Carla

    2013-05-01

    Placental acretism is an adherencial pathology associated with a high maternal morbidity and mortality rates. Antepartum diagnosis is essential to plan a proper management and reduce serious complications. Risk factors in these patients include prior cesarean sections, uterine scars and placenta previa. Second level ultrasonography may detect placental acretism with high sensitivity and specificity; magnetic resonance imaging may play a complimentary role in the diagnosis of placental acretism when ultrasonographic findings are non-conclusive, specially when determining miometrium invasion in placental acretism (incretism, percretism). This paper reports the case of a patient treated at the ABC Medical Center of Santa Fe, in her second gestation with the diagnosis of an arcuate uterus, previous cesarean section and placenta previa who presented a vaginal bleeding during pregnancy; ultrasound evaluation, in the second trimester, identified a probable placental acretism, in the third trimester, the same technology suggested placenta percreta, complimentary magnetic resonance imaging supported this diagnosis, with probable invasion to bladder, bowel and abdominal wall muscles. Imaging studies were performed at the Hospital Angeles Lomas (Maternal Fetal Clinic). A diagnosis of placenta acreta-percreta, called for a multidisciplinary surgical team, availability of blood products and other resources to face probable complications associated to the obstetrical resolution. Maternal results were optimal since histopathological evaluation reported miometrial incretism, with placental invasion millimeters away from the uterine serosa. Most ultrasonographic studies evaluating the invasion degree of the placenta have small sample sizes, generating a greater degree of false positive or false negative observations. Therefore, we agree with other authors that in all acretism cases (independent of their invasion degree), a multidisciplinary surgical team should be assembled in

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

    Yong-Hong Zhang

    2015-05-01

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

  17. Inhibition of tyrosine kinase receptors by SU6668 promotes abnormal stromal development at the periphery of carcinomas

    Farace, P; Galiè, M; Merigo, F; Daducci, A; Calderan, L; Nicolato, E; Degrassi, A; Pesenti, E; Sbarbati, A; Marzola, P

    2009-01-01

    Dynamic contrast-enhanced (albumin-Gd-DTPA) magnetic resonance imaging, performed during 2 weeks of daily administration of an inhibitor of tyrosine kinase receptors (SU6668) in an HT-29 colon carcinoma model, revealed the onset of a hyper-enhancing rim, not observed in untreated tumours. To account for tissue heterogeneity in the quantitative analysis, we segmented tumours into three subunits automatically identified by cluster analysis of the enhancement curves using a k-means algorithm. Transendothelial permeability (Kps) and fractional plasma volume (fPV) were calculated in each subunit. An avascular and necrotic region, an intermediate zone and a well-vascularised periphery were reliably identified. During untreated tumour growth, the identified sub-regions did not substantially change their enhancement pattern. Treatment with SU6668 induced major changes at tumour periphery where a significant increase of Kps and fPV was observed with respect to control tumours. Histology revealed a sub-capsular layer composed of hyper-dense viable tumour cells in the periphery of untreated tumours. The rim of viable neoplastic cells was reduced in treated tumours, and replaced by loose connective tissue characterised by numerous vessels, which explains the observed hyper-enhancement. The present data show a peripheral abnormal development of cancer-associated stroma, indicative of an adaptive response to anti-angiogenic treatment. PMID:19384298

  18. Severe vitamin D deficiency in patients with Kawasaki disease: a potential role in the risk to develop heart vascular abnormalities?

    Stagi, Stefano; Rigante, Donato; Lepri, Gemma; Matucci Cerinic, Marco; Falcini, Fernanda

    2016-07-01

    Twenty-five-hydroxyvitamin D (25(OH)-vitamin D) is crucial in the regulation of immunologic processes, but-although its deficiency has been reported in patients with different rheumatological disorders-no data are available for Kawasaki disease (KD). The goals of this study were to assess the serum levels of 25(OH)-vitamin D in children with KD and evaluate the relationship with the eventual occurrence of KD-related vascular abnormalities. We evaluated serum 25(OH)-vitamin D levels in 79 children with KD (21 females, 58 males, median age 4.9 years, range 1.4-7.5 years) in comparison with healthy sex-/age-matched controls. A significantly higher percentage of KD patients (98.7 %) were shown to have reduced 25(OH)-vitamin D levels (vitamin D than controls (9.17 ± 4.94 vs 23.3 ± 10.6 ng/mL, p vitamin D levels correlated not only with erythrosedimentation rate (p vitamin D might have a contributive role in the development of coronary artery complications observed in children with KD. PMID:25994612

  19. A double antibody radioimmunoassay specific for placental alkaline phosphatase

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

  20. Increased apoptosis and abnormal visual behavior by histone modifications with exposure to para-xylene in developing Xenopus.

    Gao, Juanmei; Ruan, Hangze; Qi, Xianjie; Guo, Xia; Zheng, Jingna; Liu, Cong; Fang, Yanxiao; Huang, Minjiao; Xu, Miao; Shen, Wanhua

    2016-09-01

    Xylene and its derivatives are raw materials widely used in industry and known to be toxic to animals. However, the mechanism underlying the neurotoxicity of para-xylene (PX) to the central nervous system (CNS) in vivo is less clear. Here, we exposed Xenopus laevis tadpoles to sub-lethal concentrations of PX during the critical period of brain development to determine the effects of PX on Xenopus development and visual behavior. We found that the abnormality rate was significantly increased with exposure to increasing concentrations of PX. In particular, the number of apoptotic cells in the optic tectum was dramatically increased with exposure to PX at 2mM. Long-term PX exposure also resulted in significant deficits in visually guided avoidance behavior. Strikingly, co-incubation with PX and d-glucuronolactone (GA) decreased the number of apoptotic cells and rescued the avoidance behavior. Furthermore, we found that the acetylation of H4K12 (H4K12ac) and the dimethylation of H3K9 (H3K9me2) in the optic tectum were significantly increased in PX-treated animals, and these effects were suppressed by GA treatment. In particular, the increase in apoptotic cells in PX-treated brains was also inhibited by GA treatment. These effects indicate that epigenetic regulation plays a key role in PX-induced apoptosis and animal behavior. In an effort to characterize the neurotoxic effects of PX on brain development and behavior, these results suggest that the neurotoxicity of PX requires further evaluation regarding the safety of commercial and industrial uses. PMID:27343828

  1. Quality assessment of a placental perfusion protocol

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

    2010-01-01

    placental perfusion model in Copenhagen including control substances. The positive control substance antipyrine shows no difference in transport regardless of perfusion media used or of terms of delivery (n=59, p<0.05). Negative control studies with FITC marked dextran correspond with leakage criteria (<3...... ml h(-1) from the fetal reservoir) when adding 2 (n=7) and 20mg (n=9) FITC-dextran/100 ml fetal perfusion media. Success rate of the Copenhagen placental perfusions is provided in this study, including considerations and quality control parameters. Three checkpoints suggested to determine success...

  2. Role of the placental Vitamin D receptor in modulating feto-placental growth in Fetal growth restriction and Preeclampsia-affected pregnancies.

    Padma eMurthi

    2016-02-01

    Full Text Available Fetal growth restriction (FGR is a common pregnancy complication that affects up to 5% of pregnancies worldwide. Recent studies demonstrate that Vitamin D deficiency is implicated in reduced fetal growth, which may be rescued by supplementation of Vitamin D. Despite this, the pathway(s by which Vitamin D modulate fetal growth remains to be investigated. Our own studies demonstrate that the Vitamin D receptor (VDR is significantly decreased in placentae from human pregnancies complicated by FGR and contributes to abnormal placental trophoblast apoptosis and differentiation and regulation of cell-cycle genes in vitro. Thus, Vitamin D signalling is important for normal placental function and fetal growth. This review discusses the association of Vitamin D with fetal growth, the function of Vitamin D and its receptor in pregnancy, as well as the functional significance of a placental source of Vitamin D in FGR. Additionally, we propose that for Vitamin D to be clinically effective to prevent and manage FGR, the molecular mechanisms of Vitamin D and its receptor in modulating fetal growth requires further investigation.

  3. Genetically induced abnormal cranial development in human trisomy 18 with holoprosencephaly: comparisons with the normal tempo of osteogenic-neural development.

    Reid, Shaina N; Ziermann, Janine M; Gondré-Lewis, Marjorie C

    2015-07-01

    Craniofacial malformations are common congenital defects caused by failed midline inductive signals. These midline defects are associated with exposure of the fetus to exogenous teratogens and with inborn genetic errors such as those found in Down, Patau, Edwards' and Smith-Lemli-Opitz syndromes. Yet, there are no studies that analyze contributions of synchronous neurocranial and neural development in these disorders. Here we present the first in-depth analysis of malformations of the basicranium of a holoprosencephalic (HPE) trisomy 18 (T18; Edwards' syndrome) fetus with synophthalmic cyclopia and alobar HPE. With a combination of traditional gross dissection and state-of-the-art computed tomography, we demonstrate the deleterious effects of T18 caused by a translocation at 18p11.31. Bony features included a single developmentally unseparated frontal bone, and complete dual absence of the anterior cranial fossa and ethmoid bone. From a superior view with the calvarium plates removed, there was direct visual access to the orbital foramen and hard palate. Both the eyes and the pituitary gland, normally protected by bony structures, were exposed in the cranial cavity and in direct contact with the brain. The middle cranial fossa was shifted anteriorly, and foramina were either missing or displaced to an abnormal location due to the absence or misplacement of its respective cranial nerve (CN). When CN development was conserved in its induction and placement, the respective foramen developed in its normal location albeit with abnormal gross anatomical features, as seen in the facial nerve (CNVII) and the internal acoustic meatus. More anteriorly localized CNs and their foramina were absent or heavily disrupted compared with posterior ones. The severe malformations exhibited in the cranial fossae, orbital region, pituitary gland and sella turcica highlight the crucial involvement of transcription factors such as TGIF, which is located on chromosome 18 and contributes

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

    Deryk Scott Beal

    2015-03-01

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

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

    Cussen, Victoria A; Mench, Joy A

    2015-01-01

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

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

    Victoria A Cussen

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

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

    Lori C Albergotti

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

  8. Placental-Derived Mesenchyme Influences Chorionic Gonadotropin and Progesterone Secretion of Human Embryonic Stem Cell-Derived Trophoblasts

    Giakoumopoulos, Maria; Siegfried, Leah M.; Dambaeva, Svetlana V.; Garthwaite, Mark A.; Glennon, M. Clay; Golos, Thaddeus G.

    2010-01-01

    Studies of early placental development in humans are difficult because of limitations on experimental material availability from the perimplantation period. We used a coculture system to determine the effects of various effector cell types on trophoblast differentiation. Enhanced green fluorescent protein (EGFP)-expressing H1 human embryonic stem cells were used in co-suspension with human term placental fibroblasts (TPFs) and dermal fibroblasts (CI2F) to form combination embryoid bodies (EBs...

  9. Placental transfer of plutonium and other actinides

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

  10. Placental Mesenchymal Dysplasia: A Case Report

    Rachna Agarwal

    2012-01-01

    Full Text Available Introduction. A rare case of histologically proven placental mesenchymal dysplasia (PMD with fetal omphalocele in a 22-year-old patient is reported. Material and Methods. Antenatal ultrasound of this patient showed hydropic placenta with a live fetus of 17 weeks period of gestation associated with omphalocele. Cordocentesis detected the diploid karyotype of the fetus. Patient, when prognosticated, choose to terminate the pregnancy in view of high incidence of fetal and placental anomalies. Subsequent histopathological examination of placenta established the diagnosis to be placental mesenchymal dysplasia. Conclusion. On clinical and ultrasonic grounds, suspicion of P.M.D. arises when hydropic placenta with a live fetus presents in second trimester of pregnancy. Cordocentesis can detect the diploid karyotype of the fetus in such cases. As this condition is prognostically better than triploid partial mole, continuation of pregnancy can sometimes be considered after through antenatal screening and patient counseling. However, a definite diagnosis of P.M.D. is made only on placental histology by absence of trophoblast hyperplasia and trophoblastic inclusions.