Amniotic fluid transcriptomics reflects novel disease mechanisms in fetuses with myelomeningocele
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE101141 | GEO | 2017/07/12
SECONDARY ACCESSION(S): PRJNA393797
REPOSITORIES: GEO
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Project description:BACKGROUND:Cell-free RNA in amniotic fluid supernatant reflects developmental changes in gene expression in the living fetus, which includes genes that are specific to the central nervous system. Although it has been previously shown that central nervous system-specific transcripts are present in amniotic fluid supernatant, it is not known whether changes in the amniotic fluid supernatant transcriptome reflect the specific pathophysiologic condition of fetal central nervous system disorders. In myelomeningocele, there is open communication between the central nervous system and amniotic fluid. OBJECTIVES:The purpose of this study was to identify molecular pathophysiologic changes and novel disease mechanisms that are specific to myelomeningocele by the analysis of amniotic fluid supernatant cell-free RNA in fetuses with open myelomeningocele. STUDY DESIGN:Amniotic fluid supernatant was collected from 10 pregnant women at the time of the open myelomeningocele repair in the second trimester (24.5±1.0 weeks); 10 archived amniotic fluid supernatant from sex and gestational age-matched euploid fetuses without myelomeningocele were used as controls (20.9±0.9 weeks). Differentially regulated gene expression patterns were analyzed with the use of human genome expression arrays. RESULTS:Fetuses with myelomeningocele had 284 differentially regulated genes (176 up- and 108 down-regulated) in amniotic fluid supernatant. Known genes that were associated with myelomeningocele (PRICKLE2, GLI3, RAB23, HES1, FOLR1) and novel dysregulated genes were identified in association with neurodevelopment and neuronal regeneration (up-regulated, GAP43 and ZEB1) or axonal growth and guidance (down-regulated, ACAP1). Pathway analysis demonstrated a significant contribution of inflammation to disease and a broad influence of Wnt signaling pathways (Wnt1, Wnt5A, ITPR1). CONCLUSION:Transcriptomic analyses of living fetuses with myelomeningocele with the use of amniotic fluid supernatant cell-free RNA demonstrated differential regulation of specific genes and molecular pathways relevant to this central nervous system disorder, which resulted in a new understanding of pathophysiologic changes. The data also suggested the importance of pathways that involve secondary disease, such as inflammation, in myelomeningocele. These newly identified pathways may lead to hypotheses that can test novel therapeutic targets as adjuncts to fetal surgical repair.
| S-EPMC5671344 | biostudies-literature
Project description:In order to characterize the differences between second trimester Down syndrome (DS) and euploid fetuses, we compared gene expression in uncultured amniotic fluid supernatant samples. We identified individually differentially expressed genes via paired t-tests in the matched samples, and a set of differentially expressed genes on chromosome 21 using Gene Set Enrichment Analysis. Functional pathway analysis of the resulting genes highlighted the importance of oxidative stress, ion transport, and G-protein signaling in the DS fetuses.
2009-05-21 | GSE16176 | GEO
Project description:To understand the molecular mechanisms underlying the congenital anomalies observed in patients with Trisomy 18, we compared gene expression in uncultured amniotic fluid supernatant samples from second trimester fetuses with Trisomy 18 and from euploid controls. Analysis of differential expression using both individual-gene and gene-set or pathway methods indicated disrupted function in ion transport, MHCII/T-cell mediated immunity, DNA repair, G-protein mediated signaling, kinases, and glycosylation. Significant down-regulation of genes involved in adrenal development was also identified in the trisomic fetuses, possibly explaining both the abnormal maternal serum estriols and the pre- and postnatal growth restriction found in this condition. We compared expression in five female fetuses with confirmed metaphase karotypes 47, XX, +18 and six female controls (46, XX). The gestational ages of the samples ranged from 17 5/7 to 20 6/7 weeks.
2010-12-03 | E-GEOD-25634 | biostudies-arrayexpress
Project description:In order to characterize the differences between second trimester Down syndrome (DS) and euploid fetuses, we compared gene expression in uncultured amniotic fluid supernatant samples. We identified individually differentially expressed genes via paired t-tests in the matched samples, and a set of differentially expressed genes on chromosome 21 using Gene Set Enrichment Analysis. Functional pathway analysis of the resulting genes highlighted the importance of oxidative stress, ion transport, and G-protein signaling in the DS fetuses. We profiled seven DS expression samples and seven controls matched for gender and approximate gestational age..
2009-05-21 | E-GEOD-16176 | biostudies-arrayexpress
Project description:Transcriptomic profiling is a crucial tool for understanding growth, development, behavior and predisposition to diseases and the development of health biomarkers. Here, we demonstrate the feasibility of transcriptomic assessment of cell-free fetal RNA in vervet monkey amniotic fluid supernatant (AFS).
2019-09-13 | GSE119908 | GEO
Project description:To understand the molecular mechanisms underlying the congenital anomalies observed in patients with Trisomy 18, we compared gene expression in uncultured amniotic fluid supernatant samples from second trimester fetuses with Trisomy 18 and from euploid controls. Analysis of differential expression using both individual-gene and gene-set or pathway methods indicated disrupted function in ion transport, MHCII/T-cell mediated immunity, DNA repair, G-protein mediated signaling, kinases, and glycosylation. Significant down-regulation of genes involved in adrenal development was also identified in the trisomic fetuses, possibly explaining both the abnormal maternal serum estriols and the pre- and postnatal growth restriction found in this condition.
2010-12-03 | GSE25634 | GEO
Project description:Piglets cloned by somatic cell nuclear transfer (SCNT) show a high incidence of malformations and a high death rate during the perinatal period. To investigate the underlying mechanisms for abnormal development of cloned pig fetuses, we compared body weight, amniotic fluid (AF) metabolome, and placental transcriptome between SCNT- and artificial insemination (AI)-derived pig fetuses. Results showed that the body weight of SCNT pig fetuses was significantly lower than that of AI pig fetuses. The identified differential metabolites between the two groups of AF were mainly involved in bile acids and steroid hormones. The levels of all detected bile acids in SCNT AF were significantly higher than those in AI AF. The increase in the AF bile acid levels in SCNT fetuses was linked with the downregulation of placental bile acid transporter expression and the abnormal development of placental folds (PFs), both of which negatively affected the transfer of bile acids from AF across the placenta into the mother's circulation. Alteration in the AF steroid hormone levels in cloned fetuses was associated with decreased expression of enzymes responsible for steroid hormone biosynthesis in the placenta. In conclusion, cloned pig fetuses undergo abnormal intrauterine development associated with alteration of bile acid and steroid hormone levels in AF, which may be due to the poor development of PFs and the erroneous expression of bile acid transporters and enzymes responsible for steroid hormone biosynthesis in the placentas.
2020-01-08 | MTBLS666 | MetaboLights
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:Background: Turner syndrome, a common sex chromosome aneuploidy, has characteristics and malformations associated with the phenotype. Fetal amniotic fluid is a complex biological material that could contribute to the understanding Turner syndrome pathogenesis. Global gene expression analysis of Turner syndrome fetal amniotic fluid supernatant was utilized to identify organ systems and specific genes that may play a role in the pathophysiologic changes that are seen in individuals with Turner syndrome. Methods: Global gene expression analysis was performed utilizing cell-free RNA from five midtrimester fetuses with Turner syndrome matched with five euploid female fetuses. Total RNA was extracted, amplified, hybridized onto GeneChipM-BM-. Human Genome U133 Plus 2.0 arrays. Network and pathway analysis of differentially expressed genes were completed. Chromosomal distribution of gene expression differences, differential expression by pathway and organ system (a M-bM-^@M-^\Turner syndrome core transcriptomeM-bM-^@M-^]), and candidate genes that could play a pathological role were identified. Results: There were 470 differentially expressed genes identified in the Turner syndrome transcriptome. The differentially expressed genes were distributed randomly across different chromosomes. Among genes on the X chromosome, XIST was down-regulated, and SHOX not differentially expressed. The most highly represented organ systems were hematologic/immune and neurologic. Increased representation of differentially expressed genes in the hematologic/immune system distinguishes the Turner syndrome transcriptome from the euploid, trisomy 18 and trisomy 21 transcriptomes previously studied in our laboratory. Manual curation of the differentially expressed gene list identified genes including NFATC3, IGFBP5, and LDLR that warrant further study. 2nd trimester amniotic fluid mRNA expression was compared between 5 Turners and 5 euploid fetuses.
2014-06-13 | E-GEOD-58435 | biostudies-arrayexpress
Project description:Background: Turner syndrome, a common sex chromosome aneuploidy, has characteristics and malformations associated with the phenotype. Fetal amniotic fluid is a complex biological material that could contribute to the understanding Turner syndrome pathogenesis. Global gene expression analysis of Turner syndrome fetal amniotic fluid supernatant was utilized to identify organ systems and specific genes that may play a role in the pathophysiologic changes that are seen in individuals with Turner syndrome. Methods: Global gene expression analysis was performed utilizing cell-free RNA from five midtrimester fetuses with Turner syndrome matched with five euploid female fetuses. Total RNA was extracted, amplified, hybridized onto GeneChip® Human Genome U133 Plus 2.0 arrays. Network and pathway analysis of differentially expressed genes were completed. Chromosomal distribution of gene expression differences, differential expression by pathway and organ system (a “Turner syndrome core transcriptome”), and candidate genes that could play a pathological role were identified. Results: There were 470 differentially expressed genes identified in the Turner syndrome transcriptome. The differentially expressed genes were distributed randomly across different chromosomes. Among genes on the X chromosome, XIST was down-regulated, and SHOX not differentially expressed. The most highly represented organ systems were hematologic/immune and neurologic. Increased representation of differentially expressed genes in the hematologic/immune system distinguishes the Turner syndrome transcriptome from the euploid, trisomy 18 and trisomy 21 transcriptomes previously studied in our laboratory. Manual curation of the differentially expressed gene list identified genes including NFATC3, IGFBP5, and LDLR that warrant further study.
2014-06-13 | GSE58435 | GEO