Project description:<p>The pregnancy vaginal microbiome contributes to risk of preterm birth, the primary cause of death in children under 5 years of age. Here we describe direct on-swab metabolic profiling by Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) for sample preparation-free characterisation of the cervicovaginal metabolome in two independent pregnancy cohorts (VMET, n = 160; 455 swabs; VMET II, n = 205; 573 swabs). By integrating metataxonomics and immune profiling data from matched samples, we show that specific metabolome signatures can be used to robustly predict simultaneously both the composition of the vaginal microbiome and host inflammatory status. In these patients, vaginal microbiota instability and innate immune activation, as predicted using DESI-MS, associated with preterm birth, including in women receiving cervical cerclage for preterm birth prevention. These findings highlight direct on-swab metabolic profiling by DESI-MS as an innovative approach for preterm birth risk stratification through rapid assessment of vaginal microbiota-host dynamics.</p><p><br></p><p><strong>Linked cross omic data sets:</strong></p><p>Meta-taxonomics data associated with this study are available in the European Nucleotide Archive (ENA): accession number <a href='https://www.ebi.ac.uk/ena/browser/view/PRJEB11895' rel='noopener noreferrer' target='_blank'>PRJEB11895</a>, <a href='https://www.ebi.ac.uk/ena/browser/view/PRJEB12577' rel='noopener noreferrer' target='_blank'>PRJEB12577</a> and <a href='https://www.ebi.ac.uk/ena/browser/view/PRJEB41427' rel='noopener noreferrer' target='_blank'>PRJEB41427</a>.</p>
Project description:The amniotic fluid (AF) cell-free (cf) RNA was shown to reflect physiological and pathological processes in pregnancy, but its value in prediction of spontaneous preterm delivery is unknown. Here we profiled cfRNA in AF samples collected from women who underwent transabdominal amniocentesis after an episode of spontaneous preterm labor and subsequently delivered within 24h (n=10) or later (n=28) in gestation. Expression of known placental single cell (sc) RNA-Seq signatures were quantified in AF cfRNA and compared between groups. Random forest models were applied to predict time to delivery after amniocentesis. There were 2385 genes differentially expressed in AF samples of women who delivered within 24 hours of amniocentesis compared to gestational age-matched samples from women who delivered after 24 hours of amniocentesis.Genes with cfRNA changes were associated with immune and inflammatory processes related to the onset of labor, and expression of placental scRNA-Seq signatures of immune cells were increased with imminent delivery. AF transcriptomic prediction models captured these effects and predicted delivery within 24 hours of amniocentesis (AUROC =0.81). These results may inform development of biomarkers for spontaneous preterm birth.
Project description:Stress urinary incontinence (SUI) greatly affects the daily life of numerous women and is closely related to a history of vaginal delivery and aging. We used vaginal balloon dilation to simulate vaginal birth injury in young and middle-aged rats to produce a SUI animal model, and found that young rats restored urethral structure and function well, but not the middle-aged rats. To identify the characteristics of cellular and molecular changes in the urethral microenvironment during the repair process of SUI. We profiled 51,690 individual female rat urethra cells from 24 and 48 weeks old, with or without simulated vaginal birth injury.
Project description:Preterm birth is a main determinant of neonatal mortality and morbidity and a major contributor to the overall mortality and burden of disease. However, precise phenotyping of the preterm birth is hampered by the imprecise definition of the clinical phenotype and complexity of the molecular phenotype due to multiple pregnancy tissue types and molecular processes that may contribute to the preterm birth. The studyâ??s aim was to comprehensively evaluate the mRNA transcriptome that characterizes preterm and term labor using precisely phenotyped samples. Expression profiles of 73 genes and non-coding RNA sequences uniquely identified the four groups of patients: delivering preterm with (PL) and without labor (PNL), term with (TL) and without labor (TNL). The largest differences in gene expression among the four groups occurred in decidua, chorion and amnion. The gene expression profiles showed suppression of chemokines expression in TNL, withdrawal of this suppression in TL, activation of multiple pathways of inflammation in PL, and an immune rejection profile in PNL. The genes constituting expression signatures showed over-representation of three putative regulatory elements in their 5â?? and 3â??UTR regions. The results suggest that pregnancy is maintained by downregulation of chemokines at the maternal-fetal interface. Withdrawal of this downregulation results in the term birth and its overriding by the activation of multiple pathways of the immune system in the preterm birth. Complications of the pregnancy associated with impairment of placental function, which necessitated premature delivery of the fetus in the absence of labor, show gene expression patterns associated with immune rejection. 183 total RNA samples from 8 tissue types collected from 35 women grouped into six categories of pregnancy outcome. One microarray replicate per sample. Other Contributors: Radek Bukowski, Sam Parry and the NICHD Genomic and Proteomic Network for Preterm Birth Research
Project description:Genome wide placental DNA methylation profiling of full term and preterm deliveries sampled from 5 full term deliveries and 4 preterm deliveries. The Illumina HumanMethylation450 Beadchip was used to obtain DNA methylation profiles across approximately 485,577 CpGs in formalin fixed samples. Samples included 4 placental tissues from 4 women with preterm delivery and 5 placental tissues from 5 women with full term delivery. 9 women's placental DNA (4 women had perterm deliveries and 5 women had full term deliveries) were hybridised to the Illumina HumanMethylation450 Beadchip
Project description:Preterm birth is multifactorial in origin with several distinct clinical phenotypes of differing etiologies, including idiopathic preterm birth. Preterm birth involves the interaction of genetic, societal and environmental factors such as nutrition, lifestyle and stress that may modulate the length of gestation via the epigenome. DNA methylation is a well-studied epigenetic modification whereby promoter methylation commonly represses gene expression and vice versa. Myometrial tissue was obtained at cesarean section at term with or without labor, preterm without labor, idiopathic preterm labor, and twin gestations with labor. Differences in the myometrial epigenomes were identified at gene promoters, CpG islands, CpG island shores and shelves, gene bodies across the genome between the groups of women with preterm labor of different phenotypes vs. normal term labor. Functional clustering analysis indicated the significantly enriched pathways of hypomethylated genes (permissive) were related to acute inflammatory and acute-phase responses. By contrast, genes that are hypermethylated (repressive) revealed enrichment for contractile fibers and cell. This study provides the first high-resolution DNA methylome of human myometrium with evidence for differences in the methylome that may relate to idiopathic preterm birth via regulation of gene expression. The findings extend previous observations that idiopathic preterm labor is associated with subclinical intrauterine infection and inflammatory pathways and point to targets for further molecular characterization of preterm delivery. Comparison of the human myometrial epigenomes in pregnancies with preterm labor of different phenotypes vs. normal term labor
Project description:Threatened preterm labour (TPTL) is the most common condition that requires hospitalisation during pregnancy. Most of these symptomatic women continue their pregnancies to term while only an estimated 5% will deliver a premature baby within ten days. Peripheral blood leukocytes are exposed to “activating signals” from reproductive tissues and may indicate the impending onset of labour. Objectives: 1) To investigate differential leukocyte gene expression in women with TPTL; and 2) to develop a gene signature to predict preterm birth (PTB) within 48 hours in symptomatic women. Design, Setting and Participants: Women clinically diagnosed with TPTL were recruited. Peripheral blood was obtained at point of admission prior to medical treatments. mRNA was extracted and microarrays (Affymetrix U133 Plus 2.0) were utilised to determine differential gene expressions between women who did (n=48) and did not (n=106) have a preterm delivery within 48 hours of hospital admission. Results: There were 394 significantly differentially expressed genes (FDR<0.05, Limma); 22 out of 30 genes chosen for qRT-PCR validation were differentially expressed (p<0.05). Total 154; 48 delivered within 48 hours of hospital admission; 106 did not deliver within 48 hours
Project description:Genome wide placental DNA methylation profiling of full term and preterm deliveries sampled from 5 full term deliveries and 4 preterm deliveries. The Illumina HumanMethylation450 Beadchip was used to obtain DNA methylation profiles across approximately 485,577 CpGs in formalin fixed samples. Samples included 4 placental tissues from 4 women with preterm delivery and 5 placental tissues from 5 women with full term delivery.
Project description:Preterm birth (PTB) is one of major causes of perinatal mortality and neonatal morbidity, but knowledge of its complex etiology is still limited. Here we present cervicovaginal fluid (CVF) protein profiles of pregnant women who subsequently delivered at spontaneous preterm or term, aiming to identify differentially expressed CVF proteins in PTB and term birth. The CVF proteome of women who sequentially delivered at preterm and term was analyzed using isobaric tags for relative and absolute quantitation (iTRAQ) coupled with two-dimensional nanoflow liquid chromatography-tandem mass spectrometry (2D-nLC-MS/MS). We compared the CVF proteome of PTB (n=5) and control subjects (term birth, n=7) using pooled control CVF (term birth, n=20) as spike-in standard. We identified 1294 CVF proteins, of which 605 were newly identified proteins. Of 990 proteins quantified in both PTB and term birth, 52 proteins were significantly up/down-regulated in PTB compared to term birth. The differentially expressed proteins were functionally associated to immune response, endopeptidase inhibitors and structural constituent of cytoskeleton. Taken together, our study provide quantitative CVF proteome profiles of pregnant women who ultimately delivered at preterm and term. These promising results could help to improve the understanding of PTB etiology and to discover biomarkers for asymptomatic PTB.
2021-09-09 | PXD021401 | Pride
Project description:Vaginal microbiota in high-risk pregnant women for spontaneous preterm birth