Serum exosomal coronin 1A and dynamin 2 as neural tube defect biomarkers

Abstract

No highly specific and sensitive biomarkers have been identified for early diagnosis of neural tube defects (NTDs). In this study, we used proteomics to identify novel proteins specific for NTDs. Our findings revealed three proteins showing differential expression during fetal development. In a rat model of NTDs, we used western blotting to quantify proteins in maternal serum exosomes on gestational days E18, E16, E14, and E12, in serum on E18 and E12, in neural tubes on E18 and E12, and in fetal neural exosomes on E18. The expression of coronin 1A and dynamin 2 was exosome-specific and associated with spina bifida aperta embryogenesis. Furthermore, coronin 1A and dynamin 2 were significantly downregulated in maternal serum exosomes (E12–E18), neural tubes, and fetal neural exosomes. Although downregulation was also observed in serum, the difference was not significant. Differentially expressed proteins were further analyzed in the serum exosomes of pregnant women during gestational weeks 12–40 using enzyme-linked immunosorbent assays. The findings revealed that coronin 1A and dynamin 2 showed potential diagnostic efficacy during gestational weeks 12–40, particularly during early gestation (12–18 weeks). Therefore, these two targets are used as candidate NTD screening and diagnostic biomarkers during early gestation. Key messages We used proteomics to identify novel proteins specific for NTDs. CORO1A and DNM2 showed exosome-specific expression and were associated with SBA. CORO1A and DNM2 were downregulated in maternal serum exosomes and FNEs. CORO1A and DNM2 showed good diagnostic efficacy for NTDs during early gestation. These two targets may have applications as NTD screening and diagnostic biomarkers.

Exploring research hotspots and future directions in neural tube defects field by bibliometric and bioinformatics analysis

“…In recent years, it has been found that exosomes may be an important way for fetus-derived molecules to enter maternal peripheral blood, and the screening of molecular markers in exosomes has also become an important way to find malformation specific molecular indicators ( Lamont et al, 2020 ). Recently CORO1A and DNM2 in serum exosomes are found as biomarkers of NTDs ( Wang et al, 2022 ).…”

Multiplexing of TMT labeling reveals folate-deficient diet-specific proteome changes in NTDs

“…In the past decades, NTD-relevant studies have been done from a transcriptome, metabolomics, and proteomics perspective ( Fan et al, 2011 ; Hansler et al, 2014 ; Liu et al, 2014 ; Puvirajesinghe and Borg, 2015 ; Yu et al, 2017 ; Wang et al, 2022 ). In transcriptomic profiles at embryonic days (E) 8.5, 9.5 and 10.5 d in a retinoic acid-induced NTD model, Yu et al, found that genes such as Bmp2, Ascl1, Olig2, Lhx1, Wnt7b, Eomes, Foxp2, Hoxb3, Gpr56, Hap1, Nkx2-1, Sez6l2, Tbx20, Nfib, Cntn1, Dcx, Gpr56, Ngrn, Ddr1, Dctn1, Dnmt3b, Ect2, Map2, Mbnl1, Meis2, Vcan, App, Nova1/2, nSR100/Srrm4, Elavl3/4, Celf3, and Rbfox1 were differentially expressed during mouse neural tube development ( Yu et al, 2017 ).…”

“…Hansler et al reported untargeted metabolite profiling in NTD-affected Lrp6 −/− whole embryos that revealed abnormal methionine regeneration, one-carbon metabolism, and antioxidant activity ( Hansler et al, 2014 ). A recent proteomic study in maternal serum exosomes identified two proteins (coronin1 A and dynamin 2) on gestational days E12 to E18 that were significantly downregulated ( Wang et al, 2022 ). Another proteomics study identified Crpm-4, Hsp-70, and calponin-3 functioning in apoptosis, folding, signal transduction, transcription, and protein synthesis that could be used as a future diagnosis and treatment methods for spina bifida ( Fan et al, 2011 ).…”

“…Mouse models are largely used to study human diseases because mouse genomes have great similarity to humans ( Krupp et al, 2012 ). A major number of neural tube malformation mouse models were constructed with RA ( Yu et al, 2017 ; Cheng et al, 2019 ; Wang et al, 2022 ; Xiaolu et al, 2023 ). Mouse neural tube closure is a process that happens between embryonic day E8.5 to E10.5 ( Copp, 2005 ; Greene and Copp, 2009 ).…”