Covid-19 Research

Original Article

Differential Proteomic Profile in the Amniotic Fluid of Pregnancies with Trisomy 21

Journal of Biomedical Research & Environmental Sciences article abstract with citation details, DOI, publication dates, subject areas, full text links, and references.

View DOI Submit Manuscript

Article Details

Publication record, authors, dates, abstract, and full text access.

Open Access
Article Type Original Article
Subject Biology Group
OCLC JBRES Record
Raquel Rodriguez-Lopez*, Yaiza Hernandez Palomares, Fatima Gimeno Ferrer, Irene Ferrer Bolufer, Carola Guzman Lujan, Otilia Zomeno Alcala, Noelia Cabrera, Maria Luz Valero Rustarazo, Jose Estardid Colom, Maria Jose Velasco Esteban, Goitzane Marcaida Benito, Amparo Secaduras Mora and Manuel M Sanchez del Pino
Issue: Volume6-Issue5
Pages: 532-544
Received: 2025-04-23
Accepted: 2025-05-27
Published: 2025-05-28

Abstract

Background: The precise analytical-clinical characterization of pregnancies carrying the most frequent aneuploidies has now been surpassed by the technical capacity to obtain their proteomic profile. Amniotic fluid contains the differential proteins related to its specific genetic alteration, representing the molecular etiopathogenesis that generates the associated phenotypes.

Method: The description of the pathognomonic proteomic profiles of amniotic fluid, obtained by Data Independent Acquisition mass spectrometry, of 785 proteins in amniotic fluid from 15 fetuses carrying the most frequent aneuploidies and 15 fetuses with normal combined risk screening.

Results: 119 proteins were clearly overrepresented in the T21 samples and 87 were decreased, 12 encoded by genes located on chromosome 21. The specific proteomic profile of pregnancies carrying Trisomy 21 was based on the combination of the COL6A1, DMBT1, HBB and PRG2 proteins. The proteomic profiles associated with T18 and T13 already suggested specific differential profiles, without reaching statistical significance.

Conclusion: The proteomic analysis of the amniotic fluid defined differentially quantified proteins related to the specific genetic alteration of Trisomy 21, as a molecular etiopathogenesis that generates associated phenotypes based on the overexpression of Extracellular Matrix (ECM) genes and adult hemoglobins, as well as a decrease in coagulation factors, the complement system and immunoglobulin fragments.

FullText HTML FullText PDF DOI: 10.37871/jbres2108 Crossmark

Certificate of Publication

Certificate of Publication

Copyright

© 2025 Rodríguez-López R, et al Distributed under Creative Commons CC-BY 4.0 OPEN ACCE Creative CommonsAttribution

How to cite this article

Rodríguez-López R, Palomares YH, Ferrer FG, Bolufer IF, Luján CG, Alcalá OZ, Cabrera N, Valero Rustarazo ML, Colom JE, Velasco Esteban MJ, Benito GM, Mora AS, del Pino MMS. Differential Proteomic Profi le in the Amniotic Fluid of Pregnancies with Trisomy 21. J Biomed Res Environ Sci. 2025 May 28; 6(5): 532-544. doi: 10.37871/jbres2108, Article ID: JBRES2108, Available at: https://www.jelsciences.com/articles/jbres2108.pdf

Subject area(s)

Molecular BiomarkersGeneticsProteomics

References

  1. Fu F, Li R, Yu Q, Wang D, Deng Q, Li L, Lei T, Chen G, Nie Z, Yang X, Han J, Pan M, Zhen L, Zhang Y, Jing X, Li F, Li F, Zhang L, Yi C, Li Y, Lu Y, Zhou H, Cheng K, Li J, Xiang L, Zhang J, Tang S, Fang P, Li D, Liao C. Application of exome sequencing for prenatal diagnosis of fetal structural anomalies: clinical experience and lessons learned from a cohort of 1618 fetuses. Genome Med. 2022 Oct 28;14(1):123. doi: 10.1186/s13073-022-01130-x. PMID: 36307859; PMCID: PMC9615232.
  2. Park HJ, Cho HY, Cha DH. The Amniotic Fluid Cell-Free Transcriptome Provides Novel Information about Fetal Development and Placental Cellular Dynamics. Int J Mol Sci. 2021 Mar 5;22(5):2612. doi: 10.3390/ijms22052612. PMID: 33807645; PMCID: PMC7961801.
  3. Fitzsimmons ED, Bajaj T. Embryology, Amniotic Fluid. 2022 Jul 19. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, Bookshelf ID: NBK541089; 2023.
  4. Vasani A, Kumar MS. Advances in the proteomics of amniotic fluid to detect biomarkers for chromosomal abnormalities and fetomaternal complications during pregnancy. Expert Rev Proteomics. 2019 Apr;16(4):277-286. doi: 10.1080/14789450.2019.1578213. Epub 2019 Feb 13. PMID: 30722712.
  5. Kolialexi A, Tounta G, Mavrou A, Tsangaris GT. Proteomic analysis of amniotic fluid for the diagnosis of fetal aneuploidies. Expert Rev Proteomics. 2011 Apr;8(2):175-85. doi: 10.1586/epr.10.112. PMID: 21501011.
  6. Cho CK, Diamandis EP. Application of proteomics to prenatal screening and diagnosis for aneuploidies. Clin Chem Lab Med. 2011 Jan;49(1):33-41. doi: 10.1515/CCLM.2011.002. Epub 2010 Oct 20. PMID: 20961197.
  7. Dagna Bricarelli F, Pierluigi M, Grasso M, Strigini P, Perroni L. Origin of extra chromosome 21 in 343 families: cytogenetic and molecular approaches. Am J Med Genet Suppl. 1990;7:129-32. doi: 10.1002/ajmg.1320370726. PMID: 1981472.
  8. del Mazo J, Pérez Castillo A, Abrisqueta JA. Trisomy 21: origin of non-disjunction. Hum Genet. 1982;62(4):316-20. doi: 10.1007/BF00304546. PMID: 6219937.
  9. Kagan KO, Wright D, Baker A, Sahota D, Nicolaides KH. Screening for trisomy 21 by maternal age, fetal nuchal translucency thickness, free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A. Ultrasound Obstet Gynecol. 2008 Jun;31(6):618-24. doi: 10.1002/uog.5331. PMID: 18461550.
  10. Demichev V, Messner CB, Vernardis SI, Lilley KS, Ralser M. DIA-NN: neural networks and interference correction enable deep proteome coverage in high throughput. Nat Methods. 2020 Jan;17(1):41-44. doi: 10.1038/s41592-019-0638-x. Epub 2019 Nov 25. PMID: 31768060; PMCID: PMC6949130.
  11. Cox J, Hein MY, Luber CA, Paron I, Nagaraj N, Mann M. Accurate proteome-wide label-free quantification by delayed normalization and maximal peptide ratio extraction, termed MaxLFQ. Mol Cell Proteomics. 2014 Sep;13(9):2513-26. doi: 10.1074/mcp.M113.031591. Epub 2014 Jun 17. PMID: 24942700; PMCID: PMC4159666.
  12. Demšar J, Curk T, Erjavec A, Gorup Č, Hočevar T, Milutinovič M, et al. Orange: Data mining toolbox in Python Journal of Machine Learning Research. 2013;14,2349–2353.
  13. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003 Nov;13(11):2498-504. doi: 10.1101/gr.1239303. PMID: 14597658; PMCID: PMC403769.
  14. Ricard-Blum S, Salza R. Matricryptins and matrikines: biologically active fragments of the extracellular matrix. Exp Dermatol. 2014 Jul;23(7):457-63. doi: 10.1111/exd.12435. PMID: 24815015.
  15. Human Phenotype Ontology Website. 2024.
  16. Bordon Y. Immune dysregulation in Down syndrome. Nat Rev Immunol. 2023 Apr;23(4):201. doi: 10.1038/s41577-023-00855-z. PMID: 36914822; PMCID: PMC10009822.
  17. von Kaisenberg CS, Brand-Saberi B, Christ B, Vallian S, Farzaneh F, Nicolaides KH. Collagen type VI gene expression in the skin of trisomy 21 fetuses. Obstet Gynecol. 1998 Mar;91(3):319-23. doi: 10.1016/s0029-7844(97)00697-2. PMID: 9491853.
  18. Quarello E, Guimiot F, Moalic JM, Simoneau M, Ville Y, Delezoide AL. Quantitative evaluation of collagen type VI and SOD gene expression in the nuchal skin of human fetuses with trisomy 21. Prenat Diagn. 2007 Oct;27(10):926-31. doi: 10.1002/pd.1803. PMID: 17602442.
  19. Weyer K, Glerup S. Placental regulation of peptide hormone and growth factor activity by proMBP. Biol Reprod. 2011 Jun;84(6):1077-86. doi: 10.1095/biolreprod.110.090209. Epub 2011 Jan 26. PMID: 21270431.
  20. Conti A, Fabbrini F, D'Agostino P, Negri R, Greco D, Genesio R, D'Armiento M, Olla C, Paladini D, Zannini M, Nitsch L. Altered expression of mitochondrial and extracellular matrix genes in the heart of human fetuses with chromosome 21 trisomy. BMC Genomics. 2007 Aug 7;8:268. doi: 10.1186/1471-2164-8-268. PMID: 17683628; PMCID: PMC1964766.
  21. Mollo N, Aurilia M, Scognamiglio R, Zerillo L, Cicatiello R, Bonfiglio F, Pagano P, Paladino S, Conti A, Nitsch L, Izzo A. Overexpression of the Hsa21 Transcription Factor RUNX1 Modulates the Extracellular Matrix in Trisomy 21 Cells. Front Genet. 2022 Mar 10;13:824922. doi: 10.3389/fgene.2022.824922. PMID: 35356434; PMCID: PMC8960062.
  22. Wilber A, Nienhuis AW, Persons DA. Transcriptional regulation of fetal to adult hemoglobin switching: new therapeutic opportunities. Blood. 2011 Apr 14;117(15):3945-53. doi: 10.1182/blood-2010-11-316893. Epub 2011 Feb 14. PMID: 21321359; PMCID: PMC3087525.
  23. Zorick TS, Mustacchi Z, Bando SY, Zatz M, Moreira-Filho CA, Olsen B, Passos-Bueno MR. High serum endostatin levels in Down syndrome: implications for improved treatment and prevention of solid tumours. Eur J Hum Genet. 2001 Nov;9(11):811-4. doi: 10.1038/sj.ejhg.5200721. PMID: 11781696.
  24. Caglayan AO, Baranoski JF, Aktar F, Han W, Tuysuz B, Guzel A, Guclu B, Kaymakcalan H, Aktekin B, Akgumus GT, Murray PB, Erson-Omay EZ, Caglar C, Bakircioglu M, Sakalar YB, Guzel E, Demir N, Tuncer O, Senturk S, Ekici B, Minja FJ, Å estan N, Yasuno K, Bilguvar K, Caksen H, Gunel M. Brain malformations associated with Knobloch syndrome--review of literature, expanding clinical spectrum, and identification of novel mutations. Pediatr Neurol. 2014 Dec;51(6):806-813.e8. doi: 10.1016/j.pediatrneurol.2014.08.025. Epub 2014 Sep 4. PMID: 25456301; PMCID: PMC5056964.
  25. Palminiello S, Kida E, Kaur K, Walus M, Wisniewski KE, Wierzba-Bobrowicz T, Rabe A, Albertini G, Golabek AA. Increased levels of carbonic anhydrase II in the developing Down syndrome brain. Brain Res. 2008 Jan 23;1190:193-205. doi: 10.1016/j.brainres.2007.11.023. Epub 2007 Nov 22. PMID: 18083150.
  26. Haseeb A, Huynh E, ElSheikh RH, ElHawary AS, Scelfo C, Ledoux DM et al. Down syndrome: a review of ocular manifestations. Ther Adv Ophthalmol. 2022;30;14:25158414221101718.
  27. Palminiello S, Kida E, Kaur K, Walus M, Wisniewski KE, Wierzba-Bobrowicz T, Rabe A, Albertini G, Golabek AA. Increased levels of carbonic anhydrase II in the developing Down syndrome brain. Brain Res. 2008 Jan 23;1190:193-205. doi: 10.1016/j.brainres.2007.11.023. Epub 2007 Nov 22. PMID: 18083150.
  28. Ryan C, Vellody K, Belazarian L, Rork JF. Dermatologic conditions in Down syndrome. Pediatr Dermatol. 2021 Nov;38 Suppl 2:49-57. doi: 10.1111/pde.14731. Epub 2021 Aug 21. PMID: 34418156.
  29. Choi JK. Hematopoietic disorders in Down syndrome. Int J Clin Exp Pathol. 2008 Jan 1;1(5):387-95. PMID: 18787621; PMCID: PMC2480572.
  30. Bordon Y. Immune dysregulation in Down syndrome. Nat Rev Immunol. 2023 Apr;23(4):201. doi: 10.1038/s41577-023-00855-z. PMID: 36914822; PMCID: PMC10009822.
  31. Veteleanu A, Pape S, Davies K, Kodosaki E, Hye A, Zelek WM, Strydom A, Morgan BP. Complement dysregulation and Alzheimer's disease in Down syndrome. Alzheimers Dement. 2023 Apr;19(4):1383-1392. doi: 10.1002/alz.12799. Epub 2022 Sep 23. PMID: 36149090; PMCID: PMC10798358.
  32. Sullivan KD, Evans D, Pandey A, Hraha TH, Smith KP, Markham N, Rachubinski AL, Wolter-Warmerdam K, Hickey F, Espinosa JM, Blumenthal T. Trisomy 21 causes changes in the circulating proteome indicative of chronic autoinflammation. Sci Rep. 2017 Nov 1;7(1):14818. doi: 10.1038/s41598-017-13858-3. PMID: 29093484; PMCID: PMC5665944.
  33. Fatoba O, Itokazu T, Yamashita T. Complement cascade functions during brain development and neurodegeneration. FEBS J. 2022 Apr;289(8):2085-2109. doi: 10.1111/febs.15772. Epub 2021 Mar 1. PMID: 33599083.
  34. Pekna M, Pekny M. The Complement System: A Powerful Modulator and Effector of Astrocyte Function in the Healthy and Diseased Central Nervous System. Cells. 2021 Jul 17;10(7):1812. doi: 10.3390/cells10071812. PMID: 34359981; PMCID: PMC8303424.
  35. Grimm J, Heckl D, Klusmann JH. Molecular Mechanisms of the Genetic Predisposition to Acute Megakaryoblastic Leukemia in Infants With Down Syndrome. Front Oncol. 2021 Mar 11;11:636633. doi: 10.3389/fonc.2021.636633. PMID: 33777792; PMCID: PMC7992977.
Publish with JBRES — Peer-reviewed, multidisciplinary Open Access with rapid review, DOI, and global visibility.
Double-Blind CrossRef DOI Discoverable
Submit Manuscript Membership