Project description:Objective: Mechanisms of preterm labour (PTL) are not fully elucidated. Cervical ripening plays an important role. We aimed to investigate possible differences in gene expression in human cervix between PTL and term labour (TL) and between PTL and preterm premature rupture of membranes (PPROM).
Project description:Early events leading to intrauterine infection remain poorly defined, but may hold the key to a therapeutic intervention for preterm delivery. To determine early molecular pathways associated with membrane weakening that may progress to preterm premature rupture of membranes (PPROM), we examined the effects of Group B Streptococcus (GBS) on fetal membranes after a choriodecidual infection.
Project description:Early events leading to intrauterine infection remain poorly defined, but may hold the key to a therapeutic intervention for preterm delivery. To determine early molecular pathways associated with membrane weakening that may progress to preterm premature rupture of membranes (PPROM), we examined the effects of Group B Streptococcus (GBS) on fetal membranes after a choriodecidual infection. Ten chronically catheterized pregnant monkeys (Macaca nemestrina) at 118-125 days gestation (term=172 days) received choriodecidual inoculation of either: 1) Group B Streptococcus (n=5) or 2) saline (n=5). Cesarean section and fetal necropsy was performed in the first week after GBS or saline inoculation regardless of labor. Macaca nemestrina chorioamnion samples were obtained at the site of inocculation immediately after cesarean delivery 4 days after GBS inoculation and 7 days after saline inoculation. RNA was extracted and profiled by microarray. Results were analyzed using single gene, Gene Set, and Ingenuity Pathway Analysis. Validation was by RT-PCR and immunohistochemistry.
Project description:Comparing miRNAs expression levels in chorioamniotic membranes from women at term in labor (TL), women at term not in labor (TNL) and women who deliverd preterm (PTLC). The goal was to see if miRNA levels are indicators of preterm delivery or spontaneous labor at term. A two-channel technology was used in this experiment in which a pooled reference RNA was used for competitive hybridization. The pooled reference was generated at Exiqon in Denmark from a mixture of several human tissues (placenta, thyroid, brain, adipose, spleen, liver, colon, skeletal muscle, ovary, kidney, heart, cervix, testes, esophagus, small intestine, prostate, trachea, thymus, bladder, lung).
Project description:Preterm labor (PTL) and preterm premature rupture of membranes (PPROM) lead to severe perinatal morbidity/mortality worldwide. Small extracellular vesicles (sEV) act in cell communication and contain microRNAs that are potential biomarkers for these complications. We aimed to compare the expression, in sEV from peripheral blood, of miRNAs between term and preterm pregnancies.
Project description:Maternal plasma samples collected longitudinally from pregnant women were profiled using SomaLogic aptamer-based assays in women with normal pregnancy and those who delivered preterm. DiagnosisGA is the gestational age at diagnosis with any disease indicated by the Group variable, and it is set to NA for normal pregnancies. In the Group variable, sPTD stands for spontaneous preterm delivery, and PPROM for preterm premature rupture of membranes. Additional longitudinal samples of the controls, including the two samples included herein, are also available and described in PMID: 28738067.
Project description:Preterm premature rupture of membranes (PPROM), which precedes approximately 30–40% of preterm births, is the main cause of neonatal morbidity, mortality, and long-term sequelae. In particular, almost half of all PPRPM cases are frequently complicated by subclinical acute inflammation in the placenta and fetal tissue, commonly named as acute histologic chorioamnionitis [HCA]. Increasing evidences suggest that HCA carries additional risks to both the pregnant women and their fetuses, including greater risk of imminent preterm birth, as well as sepsis, neurologic morbidity, and mortality in neonates. More accurate and early prenatal predictive markers (especially noninvasive ones) are urgently needed for identifying subclinical HCA in the context of PPROM.To identify potential biomarkers in the plasma that could predict histologic chorioamnionitis (HCA) in women with preterm premature rupture of membranes (PPROM), using shotgun and targeted proteomic analyses.
Project description:We performed a microarray experiment to test the hypothesis that pre-labour premature rupture of fetal membranes (PPROM) has a different underlying pathology from spontaneous premature labour with intact membranes (PTL). We thought that the different genetic signature would be detected in the cervical tissue. Our study included cervical biopsies obtained as previously described from women undergoing caesarean section (CS) following PPROM, PTL, term labour (TL) or delivering at term prior to the presentation of labour (Term no labour âTNL). After quality control of the expression arrays, any association between sample covariates was evaluated and no evidence was found of unexpected associations. The differences in expression levels for each statistical comparison were then computed. We identified genes that were differentially expressed with an adjusted pvalue < 0.01 from hypothesis testing together with a fold change >= 2. The strongest effect, i.e. the contrast with the highest number of DEGs, was observed for âTerm labour vs Term not labourâ (1,285 genes) while the contrast with the fewest DEGs was âTerm labour vs Preterm premature rupture of membranesâ (16 genes). A table showing the number of differentially expressed genes, for each comparison, can be found in the Results section of this report. We then examined the number of genes overlapping between the statistical comparisons performed (see section 2.5 of the Results) and found that the contrast âTerm labour vs Term not labourâ had a large number of DEGs in common with the five other contrasts.
Project description:Choriodecidual infection is associated with preterm premature rupture of membranes (pPROM) and preterm birth. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression and may be involved in the pathway leading to chorioamnion weakening following infection. The study objective was to determine if a miRNA profile in the chorioamnion is associated with Group B Streptococcal infection and membrane weakening.
Project description:Maternal plasma (MP) samples were collected from group 1: term not-in labor (TNIL, n=13); group 2: term in labor (TL, n= 11), group 3: preterm premature rupture of membranes (pPROM, n=8); and group 4: preterm birth (PTB, n=13). Exosomes isolated from plasma by differential density centrifugation followed by size exclusion chromatography were characterised by morphology (electron microscopy), quantity and size (nanoparticle tracking analysis and markers (western blot). A quantitative, information-independent acquisition (Sequential Windowed Acquisition of All Theoretical Mass Spectra [SWATH]) approach was used to determine the protein profile in exosomes. Ingenuity Pathway Analysis (IPA) determined pathways associated with the protein profile identified in exosomes.
