Molecular insights into myelomeningocele via proteomic analysis of amniotic fluid

IF 2.8 2区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of proteomics Pub Date : 2025-01-06 DOI:10.1016/j.jprot.2024.105372

Lucie Guilbaud , Kévin Roger , Andree Schmidt , Cerina Chhuon , Stephan Breimann , Joanna Lipecka , Sophie Dreux , Stephan A. Müller , Michel Zérah , Jérôme Larghero , Jean-Marie Jouannic , Stefan F. Lichtenthaler , Ida C. Guerrera

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引用次数: 0

Abstract

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.

Abstract Image

查看原文本刊更多论文

通过对羊水的蛋白质组学分析来了解脊膜膨出的分子。

尽管有许多关于髓脊膜膨出（MMC）胎儿治疗的研究，但这种畸形的病理生理机制仍然知之甚少。本研究旨在分析MMC胎儿羊水（AF）上清液的生化特征和蛋白质组学，探讨其产前病理生理。对来自MMC胎儿的61例心房纤颤样本与45例健康胎儿样本进行生化分析比较。对18例MMC胎儿和18例健康单胎，以及5例MMC胎儿及其健康双绒毛膜双胞胎进行蛋白质组分析。采用酶联免疫吸附试验验证蛋白质组学结果。生化分析显示，37% %的MMC病例出现肛门失禁，对照组中没有

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来源期刊

Journal of proteomics 生物-生化研究方法

CiteScore

7.10

自引率

3.00%

发文量

227

审稿时长

73 days

期刊介绍： Journal of Proteomics is aimed at protein scientists and analytical chemists in the field of proteomics, biomarker discovery, protein analytics, plant proteomics, microbial and animal proteomics, human studies, tissue imaging by mass spectrometry, non-conventional and non-model organism proteomics, and protein bioinformatics. The journal welcomes papers in new and upcoming areas such as metabolomics, genomics, systems biology, toxicogenomics, pharmacoproteomics. Journal of Proteomics unifies both fundamental scientists and clinicians, and includes translational research. Suggestions for reviews, webinars and thematic issues are welcome.