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Amniotic fluid transcriptomics reflects novel disease mechanisms in fetuses with myelomeningocele.
- Source :
-
American journal of obstetrics and gynecology [Am J Obstet Gynecol] 2017 Nov; Vol. 217 (5), pp. 587.e1-587.e10. Date of Electronic Publication: 2017 Jul 20. - Publication Year :
- 2017
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Abstract
- 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.<br />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.<br />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.<br />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).<br />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.<br /> (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Subjects :
- Adult
Case-Control Studies
Down-Regulation
Female
Fetal Therapies
Folate Receptor 1 genetics
GAP-43 Protein genetics
GTPase-Activating Proteins genetics
Gene Expression Profiling
Gestational Age
Humans
Inositol 1,4,5-Trisphosphate Receptors genetics
LIM Domain Proteins genetics
Male
Membrane Proteins genetics
Meningomyelocele surgery
Microarray Analysis
Nerve Tissue Proteins genetics
Pregnancy
Pregnancy Trimester, Second
Transcription Factor HES-1 genetics
Up-Regulation
Wnt-5a Protein genetics
Wnt1 Protein genetics
Zinc Finger E-box-Binding Homeobox 1 genetics
Zinc Finger Protein Gli3 genetics
rab GTP-Binding Proteins genetics
Amniotic Fluid metabolism
Meningomyelocele genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1097-6868
- Volume :
- 217
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- American journal of obstetrics and gynecology
- Publication Type :
- Academic Journal
- Accession number :
- 28735706
- Full Text :
- https://doi.org/10.1016/j.ajog.2017.07.022