scholarly journals Transcriptomic analysis of fetal membranes reveals pathways involved in preterm birth

2018 ◽  
Author(s):  
Silvana Pereyra ◽  
Claudio Sosa ◽  
Bernardo Bertoni ◽  
Rossana Sapiro
Keyword(s):  
Preterm Birth ◽  
Genetic Background ◽  
Fetal Membranes ◽  
South American ◽  
Common Pathway ◽  
South American Population ◽  
High Incidence ◽  
Different Populations ◽  
Term Births ◽  
Gestational Tissues

AbstractPreterm birth (PTB), defined as infant delivery before 37 weeks of completed gestation, results of the interaction of both genetic and environmental components and constitutes a complex multifactorial syndrome. Transcriptome analysis of PTB has proved challenging because of the multiple causes of PTB and the numerous maternal and fetal gestational tissues that must interact to facilitate parturition. A common pathway of labor and PTB may be the activation of fetal membranes. In this work, chorioamnion membranes from severe preterm and term fetus were analyzed using RNA sequencing. A total of 270 genes were differentially expressed (DE): 252 were up-regulated and 18 were down-regulated in the severe preterm compared to the term births. We found great gene expression homogeneity in the control samples, and not in severe preterm samples. In this work, we identified up-regulated pathways that were previously suggested as leading to PTB like immunological and inflammatory paths. New pathways that were not identified in preterm like the hemopoietic path appeared up-regulated in preterm membranes. A group of 18 down-regulated genes discriminates between term and severe preterm cases. These genes potentially characterize a severe preterm transcriptome pattern and therefore are candidate genes for understanding the syndrome. Some of the down-regulated genes are involved in the nervous system, morphogenesis (WNT-1, DLX5, PAPPA2) and ion channel complexes (KCNJ16, KCNB1), making them good candidates as biomarkers of PTB.The identification of this DE gene pattern may help to develop a multi-gene disease classifier. These markers were generated in an admixtured South American population where PTB has a high incidence. Since genetic background may impact differentially in different populations it is mandatory to include populations like South American and African ones that are usually excluded from high throughput approaches. These classifiers should be compared to those in other populations to get a global landscape of PTB.

scholarly journals Dietary Flavonoids as Therapeutics for Preterm Birth: Luteolin and Kaempferol Suppress Inflammation in Human Gestational TissuesIn Vitro

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Courtney Wall ◽  
Ratana Lim ◽  
Marin Poljak ◽  
Martha Lappas
Keyword(s):  
Preterm Birth ◽  
Proinflammatory Cytokines ◽  
Binding Activity ◽  
Fetal Membranes ◽  
Myometrial Cells ◽  
Uterine Contractions ◽  
Dna Binding Activity ◽  
Gestational Tissues ◽  
Dietary Flavonoids

Infection/inflammation is commonly associated with preterm birth (PTB), initiating uterine contractions and rupture of fetal membranes. Proinflammatory cytokines induce matrix metalloproteinases (MMPs) that degrade the extracellular matrix (ECM) and prostaglandins which initiate uterine contractions. Nuclear factor-κB (NF-κB) and activator-protein- (AP-)1 have key roles in the formation of these prolabour mediators. In nongestational tissues, dietary flavonoids such as luteolin and kaempferol inhibit NF-κB, AP-1, and their downstream targets. The aim of this study was to determine if luteolin and kaempferol reduce infection-induced prolabour mediators in human gestational tissues. Fetal membranes were incubated with LPS, and primary amnion cells and myometrial cells were incubated with IL-1βin the absence or presence of luteolin or kaempferol. Luteolin and kaempferol significantly reduced LPS-induced secretion of proinflammatory cytokines (IL-6 and IL-8) and prostaglandins (PGE2and PGF2α) in fetal membranes, IL-1β-induced COX-2 gene expression and prostaglandin production in myometrium, and IL-1β-induced MMP-9 activity in amnion and myometrial cells. Luteolin and kaempferol decreased IL-1β-induced NF-κB p65 DNA binding activity and nuclear c-Jun expression. In conclusion, luteolin and kaempferol inhibit prolabour mediators in human gestational tissues. Given the central role of inflammation in provoking preterm labour, phytophenols may be a therapeutic approach to reduce the incidence of PTB.

Markers of protein synthesis are increased in fetal membranes and myometrium after human labour and delivery

2018 ◽  
Vol 30 (2) ◽  
pp. 313 ◽  
Author(s):  
Stella Liong ◽  
Martha Lappas
Keyword(s):  
Protein Synthesis ◽  
Preterm Birth ◽  
Protein Kinase ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Fetal Membranes ◽  
Specific Chemical ◽  
Polycytidylic Acid ◽  
Human Labour ◽  
Gestational Tissues

Preterm birth remains one of the leading causes of neonatal death. Inflammation and maternal infection are two of the leading aetiological factors for preterm birth. Labour is associated with increased production of proinflammatory cytokines, chemokines and prolabour mediators in human gestational tissues. In non-gestational tissues, synthesis of proinflammatory and prolabour mediators is regulated by components of the protein synthesis machinery. Therefore, in the present study we investigated the effect of human labour on the expression of three protein synthesis markers, namely eukaryotic elongation factor 2 kinase (EEF2K), mitogen-activated protein kinase interacting protein kinase 1 (MKNK1) and eukaryotic translation initiation factor 4E (EIF4E), and their role in regulating inflammation in human gestational tissues. In fetal membranes and myometrium, EEF2K expression was significantly lower, whereas MKNK1 expression was significantly higher withterm and preterm labourcompared to term nolabour. In contrast, EIF4E expression did not change in fetal membranes or myometrium with labour. In primary myometrial cells, loss-of-function studies using specific chemical inhibitors of EEF2K (A484954) and MKNK1 (CGP57380) demonstrated that MKNK1, but not EEF2K, was required for polyinosinic-polycytidylic acid (poly(I:C); a viral double-stranded RNA mimetic) and interleukin (IL)-1β-induced production of IL6, C-X-C motif chemokine ligand 8 (CXCL8), prostaglandin-endoperoxide synthase 2 (PTGS2) and prostaglandin F2α. In conclusion, spontaneous term and preterm labour is associated with decreased EEF2K and increased MKNK1 expression in fetal membranes and myometrium. Moreover, MKNK1 is involved in the genesis of proinflammatory and prolabour mediators that is mediated by inflammation or infection. However, further studies are required to elucidate the role of EEF2K in human labour.

Targeting bromodomain-containing proteins to prevent spontaneous preterm birth

2019 ◽  
Vol 133 (23) ◽  
pp. 2379-2400 ◽  
Author(s):  
Ratana Lim ◽  
Caitlyn Nguyen-Ngo ◽  
Martha Lappas
Keyword(s):  
Preterm Birth ◽  
Preterm Labor ◽  
Selective Inhibition ◽  
Clinical Samples ◽  
Fetal Membranes ◽  
Spontaneous Preterm Birth ◽  
Protein Inhibition ◽  
Decidual Cells ◽  
Gestational Tissues ◽  
Human And Mouse

Abstract Preterm birth is a global healthcare challenge. Spontaneous preterm birth (sPTB) is commonly caused by inflammation, yet there are currently no effective therapies available. The Bromodomain and Extra-Terminal motif (BET) proteins, Bromodomain-containing protein (Brd) 2 (Brd2), Brd3 and Brd4 regulate inflammation in non-gestational tissues. The roles of Brd2–4 in human pregnancy are unknown. Using human and mouse models, the present study has identified the Brd proteins part of the process by which inflammation induces parturition. Using human clinical samples, we demonstrate that labor and infection increase the expression of Brds in the uterus and fetal membranes. In primary human myometrial, amnion and decidual cells, we found that global Brd protein inhibition, as well as selective inhibition of Brds, suppressed inflammation-induced expression of mediators involved in myometrial contractions and rupture of fetal membranes. Importantly, studies in the mouse model demonstrate that the pan-Brd inhibitor JQ1 reduced intrauterine inflammation induced by bacterial endotoxin LPS as well as decreasing the effectiveness of LPS to induce parturition. These results implicate BET proteins as novel therapeutic targets for reducing inflammation associated with spontaneous preterm labor.

Infoveillance based on Social Sensors to Analyze the impact of Covid19 in South American Population (Preprint)

2020 ◽  
Author(s):  
Josimar E. Chire Saire
Keyword(s):  
Text Mining ◽  
Electronic Communication ◽  
Spanish Speakers ◽  
South American ◽  
South American Population ◽  
The People ◽  
Data Source ◽  
The Impact ◽  
General Concern ◽  
Social Sensors

BACKGROUND Infoveillance is an application from Infodemiology field with the aim to monitor public health and create public policies. Social sensor is the people providing thought, ideas through electronic communication channels(i.e. Internet). The actual scenario is related to tackle the covid19 impact over the world, many countries have the infrastructure, scientists to help the growth and countries took actions to decrease the impact. South American countries have a different context about Economy, Health and Research, so Infoveillance can be a useful tool to monitor and improve the decisions and be more strategical. The motivation of this work is analyze the capital of Spanish Speakers Countries in South America using a Text Mining Approach with Twitter as data source. The preliminary results helps to understand what happens two weeks ago and opens the analysis from different perspectives i.e. Economics, Social. OBJECTIVE Analyze the behaviour of South American Capitals in front of covid19 pandemics and show the helpfulness of Text Mining Approach for Infoveillance tasks. METHODS Text Mining process RESULTS - Argentina and Venezuela capitals are the biggest number of post during this period, opposite with Bolivia, Ecuador and Uruguay. - Most relevant users are related to mass media like radio, television or newspapers. - There is a general concern about covid19 but every country talks about different areas: Economics, Health, Environmental Impact. CONCLUSIONS Infoveillance based on Social Sensors with data coming from Twitter can help to understand the trends on the population of the capitals. Besides, it is necessary to filter the posts for processing the text and get insights about frequency, top users, most important terms. This data is useful to analyse the population from different approaches. INTERNATIONAL REGISTERED REPORT RR2-https://doi.org/10.1101/2020.04.06.20055749

scholarly journals Polymorphisms in the DAD1 and OXA1L genes are associated with asthma and atopy in a South American population

2018 ◽  
Vol 101 ◽  
pp. 294-302 ◽  
Author(s):  
Anaque de Oliveira Pires ◽  
Gerson de Almeida Queiroz ◽  
Milca de Jesus Silva ◽  
Raimon Rios da Silva ◽  
Hugo Bernardino Ferreira da Silva ◽  
...  
Keyword(s):  
South American ◽  
American Population ◽  
South American Population

scholarly journals Impact of preconception vaginal microbiota on women’s risk of spontaneous preterm birth: protocol for a prospective case-cohort study

BMJ Open ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. e035186 ◽  
Author(s):  
Erica M Lokken ◽  
Kishorchandra Mandaliya ◽  
Sujatha Srinivasan ◽  
Barbra A Richardson ◽  
John Kinuthia ◽  
...  
Keyword(s):  
Cohort Study ◽  
Preterm Birth ◽  
Umbilical Cord ◽  
Bacterial Species ◽  
Vaginal Microbiota ◽  
Fetal Membrane ◽  
Fetal Membranes ◽  
Rrna Gene ◽  
Spontaneous Preterm Birth ◽  
Increased Risk

IntroductionBacterial vaginosis (BV) and vaginal microbiota disruption during pregnancy are associated with increased risk of spontaneous preterm birth (SPTB), but clinical trials of BV treatment during pregnancy have shown little or no benefit. An alternative hypothesis is that vaginal bacteria present around conception may lead to SPTB by compromising the protective effects of cervical mucus, colonising the endometrial surface before fetal membrane development, and causing low-level inflammation in the decidua, placenta and fetal membranes. This protocol describes a prospective case-cohort study addressing this hypothesis.Methods and analysisHIV-seronegative Kenyan women with fertility intent are followed from preconception through pregnancy, delivery and early postpartum. Participants provide monthly vaginal specimens during the preconception period for vaginal microbiota assessment. Estimated date of delivery is determined by last menstrual period and first trimester obstetrical ultrasound. After delivery, a swab is collected from between the fetal membranes. Placenta and umbilical cord samples are collected for histopathology. Broad-range 16S rRNA gene PCR and deep sequencing of preconception vaginal specimens will assess species richness and diversity in women with SPTB versus term delivery. Concentrations of key bacterial species will be compared using quantitative PCR (qPCR). Taxon-directed qPCR will also be used to quantify bacteria from fetal membrane samples and evaluate the association between bacterial concentrations and histopathological evidence of inflammation in the fetal membranes, placenta and umbilical cord.Ethics and disseminationThis study was approved by ethics committees at Kenyatta National Hospital and the University of Washington. Results will be disseminated to clinicians at study sites and partner institutions, presented at conferences and published in peer-reviewed journals. The findings of this study could shift the paradigm for thinking about the mechanisms linking vaginal microbiota and prematurity by focusing attention on the preconception vaginal microbiota as a mediator of SPTB.

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