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001     275969
005     20250126000535.0
024 7 _ |a 10.1016/j.jprot.2024.105372
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024 7 _ |a pmid:39778765
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024 7 _ |a 1874-3919
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024 7 _ |a 1876-7737
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037 _ _ |a DZNE-2025-00165
041 _ _ |a English
082 _ _ |a 540
100 1 _ |a Guilbaud, Lucie
|b 0
245 _ _ |a Molecular insights into myelomeningocele via proteomic analysis of amniotic fluid.
260 _ _ |a New York, NY [u.a.]
|c 2025
|b Elsevier
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520 _ _ |a Despite numerous studies on fetal therapy for myelomeningoceles (MMC), the pathophysiology of this malformation remains poorly understood. This study aimed to analyze the biochemical profile and proteome of amniotic fluid (AF) supernatants from MMC fetuses to explore the prenatal pathophysiology. Biochemical analysis of 61 AF samples from MMC fetuses was compared with 45 healthy fetuses' samples. Proteome analysis was conducted in 18 MMC and 18 healthy singleton fetuses, and in 5 dichorionic pregnancies with MMC fetuses and their healthy co-twins. ELISA tests were used to validate proteome results. Biochemical analysis revealed anal incontinence in 37 % of MMC cases, absent in controls (p < 0.0001). Proteomics identified 2453 quantified proteins with 39 significantly up-regulated and 10 down-regulated in the MMC group. Up-regulated proteins included ectodomains of CHL1, APLP1, SEZ6, SEZ6L, known targets of the protease BACE1. We explored the overlap of neonatal cerebrospinal fluid (CSF) and AF proteome and highlighted 411 proteins in common, mostly upregulated in MMC AF compared to controls. Our study thoroughly characterizes the AF proteome and reveals numerous proteins to be changed as a consequence of MMC. Many of these proteins are typical constituents of CSF. No difference in AF inflammation markers were observed between MMC and healthy fetuses. SIGNIFICANCE: This study provides good evidence that neuroepithelial destruction in MMC is independent of inflammation or presumed meconium toxicity.
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650 _ 7 |a Amniotic fluid
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650 _ 7 |a BACE1
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650 _ 7 |a Myelomeningocele
|2 Other
650 _ 7 |a Pathophysiology
|2 Other
650 _ 7 |a Proteomics
|2 Other
650 _ 7 |a Spina bifida
|2 Other
700 1 _ |a Roger, Kévin
|b 1
700 1 _ |a Schmidt, Andree
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700 1 _ |a Chhuon, Cerina
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700 1 _ |a Breimann, Stephan
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700 1 _ |a Lipecka, Joanna
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700 1 _ |a Dreux, Sophie
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700 1 _ |a Müller, Stephan A
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700 1 _ |a Zérah, Michel
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700 1 _ |a Larghero, Jérôme
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700 1 _ |a Jouannic, Jean-Marie
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700 1 _ |a Lichtenthaler, Stefan F
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700 1 _ |a Guerrera, Ida C
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773 _ _ |a 10.1016/j.jprot.2024.105372
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|t Journal of proteomics
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856 4 _ |u https://pub.dzne.de/record/275969/files/DZNE-2025-00165%20SUP.zip
856 4 _ |u https://pub.dzne.de/record/275969/files/DZNE-2025-00165_Restricted.pdf
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