Novel Placental Biomarker Shows Predictive Potential for Spontaneous Preterm Labor
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ABSTRACT:
PROVIDER: PRJNA1073437 | ENA |
REPOSITORIES: ENA
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Project description:Objective: Human parturition involves many events among mother, fetus, and placenta, and the initiation of these events is the consequence of activation of a series of endocrine and immune responses. Multiple underlying pathways account for the cascade of events that culminate in spontaneous preterm labor. In this study, we aimed to characterize these signaling pathways of placental origin at molecular levels. Study design: We used single-cell RNA-sequencing (sc-RNA-seq) analysis to probe transcriptional heterogeneity in human placenta delivered at preterm or term and then used RNA in situ hybridization (RNA-ISH) assay on formalin-fixed paraffin-embedded (FFPE) placental tissues to validate these results. Results: By using sc-RNA-seq on villous cytotrophoblast (CTB) isolated from a preterm placenta, we found that signaling pathways implicated in the initiation of term or preterm labor including ferroptosis, kisspeptin (KISS1), and senescence were constitutively activated in distinct cellular clusters of these trophoblastic stem cells. RNA-ISH-based spatial gene expression profiling in FFPE tissues revealed that pregnancy-specific beta-1-glycoprotein 4 (PSG4), a potent molecular driver for cellular aging, was significantly increased in preterm placentas (N = 30) compared to their full-term counterparts (N = 9). Furthermore, PSG4 mRNA signals were predominantly detected in the villous syncytiotrophoblast and the discontinuous monolayer of CTB as well as the intervillous space where maternal blood circulates. Conclusion: Our study provides strong support for PSG4 overexpression serving as a biomarker for pregnant women at risk for preterm delivery, which can allow for the development of timely and clinical preventive strategies.
2025-02-04 | GSE255051 | GEO
Project description:Preterm birth, defined as delivery before the 37th week of gestation, is the most common cause of neonatal mortality and the second leading cause of death in children under five years of age. Preterm birth is associated with immediate and long term morbidity as well as growth and developmental delay. Currently there is no treatment that can prevent or block preterm labor. In order to identify the molecular regulators of preterm spontaneous labor in the human myometrium, we studied the gene expression profiles of samples with Preterm Spontaneous Labour (PSL) and compared them with the gene expression profiles of samples with Preterm No Labor (PNL).
2021-04-29 | GSE134447 | GEO
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.
2021-10-01 | GSE166956 | GEO
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
2017-05-04 | E-GEOD-71123 | biostudies-arrayexpress
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.
2024-03-13 | GSE243831 | GEO
Project description:The study evaluated the differences in the transcriptomic in myometrium from women in spontaneous labor and not in labor, both at term.
2021-08-18 | GSE178781 | GEO
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.
2017-05-04 | GSE71123 | GEO
Project description:The amniotic fluid cell-free transcriptome in spontaneous preterm labor
| PRJNA702468 | ENA
Project description:Distinct processes govern the transition from myometrial quiescence to activation during both term and preterm labor. We sought the specific gene sets responsible for initiating term and preterm labor, along with a core set of effector genes necessary for labor independent of gestational age and the underlying trigger. The Effector Gene Set consisted of 49 genes present in both preterm and term labor but absent from non-labor samples. 122 genes were specific to preterm labor (Preterm Initiator Set) and 229 to term labor (Term Initiator Set). The Term Initiator and the Effector Sets reflected predominantly inflammatory processes. Surprisingly, the Preterm Initiator Gene Set reflected molecular and biological events almost exclusive of inflammation. Preterm and term labor differ dramatically in their unique, initiator gene profiles, suggesting alternative pathways underlie these events. Inflammatory processes are ubiquitous to the Term Initiator and the Effector Gene Sets, supporting the idea term parturition is an inflammatory process. The absence of inflammatory processes in the Preterm Initiator Set suggests inflammation is secondary to processes triggering spontaneous preterm birth, and could explain the lack of therapeutic efficacy associated with anti inflammatory/antibiotic regimens. Keywords: myometrial gene expression, preterm versus term labor
2008-09-27 | GSE9159 | GEO
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).
2008-10-01 | E-TABM-469 | biostudies-arrayexpress