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Amniotic fluid transcriptomics reflects novel disease mechanisms in fetuses with myelomeningocele
- Source :
- American Journal of Obstetrics and Gynecology. 217:587.e1-587.e10
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
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. 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 , RAB2 3, HES1 , FOLR1 ) and novel dysregulated genes were identified in association with neurodevelopment and neuronal regeneration (up-regulated, GAP4 3 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.
- Subjects :
- Adult
Male
0301 basic medicine
medicine.medical_specialty
Meningomyelocele
Amniotic fluid
Central nervous system
Down-Regulation
Gestational Age
Nerve Tissue Proteins
Inflammation
Wnt1 Protein
Biology
Article
Wnt-5a Protein
Andrology
Transcriptome
03 medical and health sciences
GAP-43 Protein
Pregnancy
Zinc Finger Protein Gli3
Internal medicine
Gene expression
medicine
Humans
Inositol 1,4,5-Trisphosphate Receptors
Folate Receptor 1
Fetal Therapies
Fetus
Gene Expression Profiling
GTPase-Activating Proteins
Wnt signaling pathway
Membrane Proteins
Zinc Finger E-box-Binding Homeobox 1
Obstetrics and Gynecology
LIM Domain Proteins
Amniotic Fluid
Microarray Analysis
Up-Regulation
WNT5A
030104 developmental biology
Endocrinology
medicine.anatomical_structure
rab GTP-Binding Proteins
Case-Control Studies
Pregnancy Trimester, Second
Transcription Factor HES-1
Female
medicine.symptom
Subjects
Details
- ISSN :
- 00029378
- Volume :
- 217
- Database :
- OpenAIRE
- Journal :
- American Journal of Obstetrics and Gynecology
- Accession number :
- edsair.doi.dedup.....d34edc0c23ddcf092cc124abb23f5291