Project description:We compared fetal membrane tissue from preterm labor deliveries to fetal tissue from preterm labor with preterm prelabor rupture of membranes (PPROM) deliveries to further explore the concept that spontaneous preterm birth can result from the initializing of two separate but overlapping pathological events. Chorioamnion, separated into amnion and chorion, was collected from gestationally age-matched cases and controls within 15 minutes of birth, and analyzed using RNA sequencing. In our study, transcriptome analysis of preterm fetal membranes revealed distinct differentially expressed genes for PPROM, separate from preterm labor. This study is the first to report transcriptome data that reflects the individual pathophysiology of amnion and chorion tissue from PPROM deliveries.
Project description:Approximately 25% of all preterm births are due to preterm premature rupture of membranes. Mice deficient in proteoglycans biglycan (Bgn) and decorin (Dcn) display abnormal fetal membranes and increased incidence of preterm birth. We conducted RNA-Seq to profile fetal membranes and identify molecular pathways that may lead to preterm birth in double knockout (DKO) mice (Bgn −/−; Dcn −/− ) compared to wild-type (WT) at two different gestational stages, E12 and E18 (n=3 in each group). 3264 transcripts were differentially regulated in E18 DKO vs. WT fetal membranes, and 96 transcripts differentially regulated in E12 DKO vs. WT fetal membranes (FDR<0.05, log 2 FC≥1). Differentially regulated transcripts in E18 DKO fetal membranes were significantly enriched for genes involved in cell cycle regulation, extracellular matrix-receptor interaction, and the complement cascade. 50 transcripts involved in the cell cycle were altered in E18 DKO fetal membranes (40↓, 10↑, FDR<0.05), including p21 and p57 (↑), and Tgfb2, Smad3, CycA, Cdk1, and Cdk2(↓). Thirty-one transcripts involved in the complement cascade were altered (11↓, 20↑, FDR<0.05) in E18 DKO fetal membranes, including C1q, C2, and C3 (↑). Differentially expressed genes in the top three molecular pathways (1) showed evidence of negative or purifying selection, and (2) were significantly enriched (Z-score>10) for transcription factor binding sites for Nr2f1 at E18. We propose that in DKO mice, cell cycle arrest results in lack of cell proliferation in fetal membranes, inability to contain the growing fetus, and preterm birth.
Project description:To characterize the molecular profile of the chorioamniotic membranes of preterm neonates with and without neurocognitive impairment at 18-24 months and (2) to determine if neonates who developed neurocognitive impairment can be identified at birth. Paired two-group design
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:To characterize the molecular profile of the chorioamniotic membranes of preterm neonates with and without neurocognitive impairment at 18-24 months and (2) to determine if neonates who developed neurocognitive impairment can be identified at birth.
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:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
Project description:Preterm birth is a multifactorial condition defined as birth less than 37 weeks of gestation. This study aimed to identify early pregnancy biomarkers from maternal genome-wide and transcriptome-wide data of women experiencing two types of spontaneous PTB (sPTB): spontaneous preterm birth (SPTB) and preterm premature rupture of membranes (PPROM). Whole blood samples were obtained from women with singleton pregnancies (N=567) recruited at the Liverpool Women’s Hospital at 16 and 20 weeks of gestation. Women with a previous history of sPTB pregnancies <34 weeks were categorised on their index pregnancy outcome as spontaneous preterm birth (SPTB) and preterm premature rupture of membranes (PPROM) or high-risk term control (HTERM, ≥37 weeks). Women with no history of SPTB/PPROM and delivered at term were LTERM (≥39 weeks of gestation). DNA was genotyped on the UK Biobank Axiom™ array (Applied Biosystems™, Thermo Fisher Scientific) and RNA who processed using the Clariom™ D Human assay (Thermo Fisher Scientific). Genome-wide association analysis, differential expression analysis and expression quantitative trait loci (eQTL) were completed.
Project description:Myometrial biopsies were collected from 31 women undergoing primary cesarean sections and were carefully phenotyped with respect to gestational age (GA), circumstances of labor onset, and clinical status at the start and end of the intervention. Cases were aggregated into groups as follows: Group 1: term birth following spontaneous onset of term labor (TL, n=5); Group 2: term birth by elective cesarean section not in labor (TNL, n=5); Group 3: PTB following spontaneous preterm labor with intact membranes (n=6); Group 4: preterm birth following PPROM (n=8); and Group 5: provider-initiated preterm birth in the absence of active labor contractions, cervical dilation or membrane rupture (n=7). Additional phenotyping of cases spontaneously committed to PTBs (Groups 3 and 4) involved presence or absence of Triple I based on cultures of amniotic fluid obtained via clinically-indicated amniocentesis. RNAs were profiled using second generation RNA sequencing.