Cellular stress proteins in the proteome of serum from mothers carrying aneuploid fetuses
Main Article Content
Abstract
Background: Aneuploidy is a genetic condition characterized by an abnormal number of chromosomes in a cell. The reduced fitness of most aneuploid cells led to the hypothesis that aneuploidy induces stress due to imbalanced global gene expression. In this study, we used proteomic analysis to analyze possible cellular stress mechanisms by comparing the serum of pregnant women between those carrying aneuploid fetuses and those carrying normal fetuses. Materials and methods: Women in their second trimester of pregnancy carrying an aneuploid fetus or a healthy fetus, as determined by ultrasound, were invited to participate in the study. The women’s serum proteome was analyzed using a UPLC-QTof/MS/MS system. We identified differentially accumulated proteins between the groups and generated a network of proteins that were up accumulated in the aneuploidy group. Results: The proteome comparison between five pregnant women carrying a fetus with aneuploidy (two with T13 and three with T18) and ten mothers carrying a normal fetus (mean gestational age:18.5 weeks) yielded 16 differentially accumulated proteins, eight from each group. The down-accumulated proteins were zinc finger protein 13 (which contains a CCCH domain), layilin, C-C chemokine receptor type 10, transcription factor TFIIB, TATA Box Binding Protein, G protein-coupled receptor, Malate dehydrogenase (MDH1), and Heavy chain mu. The up-accumulated proteins were ATP-synthase, Helicase, TAP1, Rho GTPase-activating protein 28, Microtubule-Associated Protein 4, Serotonin transporter, Plasma membrane transporter, and Interferon gamma receptor 1. Conclusion: We have demonstrated differential expressions of proteins that interfere with cell cycle, energy production, and immunity in the serum of mothers carrying aneuploid fetuses, which may represent cell stress or an aberrant cell cycle due to the disrupted stoichiometry of genes and proteins triggered by the fetal aneuploid tissues. Also, the protein networks of overexpressed proteins showed complex evolution in many biochemical pathways of the central nervous system.
Keywords:
Aneuploidies. Patau syndrome, Edwards syndrome; Prenatal proteomic profile; Maternal serum; nanoUPLC-MS/MS.
Article Details
How to Cite
URIARTE, G. Arelí Lopez et al.
Cellular stress proteins in the proteome of serum from mothers carrying aneuploid fetuses.
Medical Research Archives, [S.l.], v. 14, n. 1, jan. 2026.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/7199>. Date accessed: 03 feb. 2026.
doi: https://doi.org/10.18103/mra.v14i1.7199.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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6. Satgé D, Nishi M, Sirvent N, Vekemans M, Chenard MP, Barnes A. A tumor profile in Patau syndrome (trisomy 13). Am J Med Genet A. 2017 Aug;173(8):2088-2096. doi: 10.1002/ajmg.a.38294. Epub 2017 May 25. PMID: 28544599.
7. Cereda A, Carey JC. The trisomy 18 syndrome. Orphanet J Rare Dis. 2012 Oct 23;7:81. doi: 10.11 86/1750-1172-7-81. PMID: 23088440; PMCID: PMC3520824.Jason M. Sheltzer [email protected]
8. Cho WK. Lifelong medical challenges and immunogenetics of Turner syndrome. Clin Exp Pediatr. 2024 Nov;67(11):560-568. doi: 10.3345/cep.2024.0 0430. Epub 2024 Jul 31. PMID: 39091155; PMCID: PMC11551602.
9. Romero R, Erez O, Maymon E, Chaemsaithong P, Xu Z, Pacora P, Chaiworapongsa T, Done B, Hassan SS, Tarca AL. The maternal plasma proteome changes as a function of gestational age in normal pregnancy: a longitudinal study. Am J Obstet Gynecol. 2017 Jul;217(1):67.e1-67.e21. doi: 10.1016/j.ajog.2 017.02.037. Epub 2017 Mar 3. PMID: 28263753; PMCID: PMC5813489.
10. Eduardo M. Torres, Maitreya J. Dunham, and Angelika Amon Transcriptional consequences of aneuploidy, July 16, 2012 109 (31) 12644-12649 https://doi.org/10.1073/pnas.1209227109
11. Dürrbaum M, Storchová Z. Effects of aneuploidy on gene expression: implications for cancer. FEBS J. 2016 Mar;283(5):791-802. doi: 10.1111/febs.135 91. Epub 2015 Dec 8. PMID: 26555863.
12. López Uriarte GA, Burciaga Flores CH, Torres de la Cruz VM, Medina Aguado MM, Gómez Puente VM, Romero Gutiérrez LN, Martínez de Villarreal LE. Proteomic profile of serum of pregnant women carring a fetus with Down syndrome using nano uplc Q-tof ms/ms technology. J Matern Fetal Neonatal Med. 2018 Jun;31(11):1483-1489. doi: 10.1080/14 767058.2017.1319923. Epub 2017 May 3. PMID: 28412848.).
13. Zhang S, Wang R, Huang C, Zhang L, Sun L. Modulation of Global Gene Expression by Aneuploidy and CNV of Dosage Sensitive Regulatory Genes. Genes (Basel). 2021 Oct 12;12(10):1606. doi: 10.33 90/genes12101606. PMID: 34681000; PMCID: PMC8535535).
14. Kojima S, Cimini D. Aneuploidy and gene expression: is there dosage compensation? Epigenomics. 2019 Dec;11(16):1827-1837. doi: 10.2217/epi-2019-0135. Epub 2019 Nov 22. PMID: 31755744; PMCID: PMC7132608.
15. Borck G, Hög F, Dentici ML, Tan PL, Sowada N, Medeira A, Gueneau L, Thiele H, Kousi M, Lepri F, Wenzeck L, Blumenthal I, Radicioni A, Schwarzenberg TL, Mandriani B, Fischetto R, Morris-Rosendahl DJ, Altmüller J, Reymond A, Nürnberg P, Merla G, Dallapiccola B, Katsanis N, Cramer P, Kubisch C. BRF1 mutations alter RNA polymerase III-dependent transcription and cause neurodevelopmental anomalies. Genome Res. 2015 Feb;25(2):155-66. doi: 10.1101/gr.176925.114. Epub 2015 Jan 5. Erratum in: Genome Res. 2015 Apr;25(4):609. PMID: 25561 519; PMCID: PMC4315290.
16. Zhou W, Wang H, Yang Y, Guo F, Yu B, Su Z. Trophoblast Cell Subtypes and Dysfunction in the Placenta of Individuals with Preeclampsia Revealed by Single Cell RNA Sequencing. Mol Cells. 2022 May 31;45(5):317-328. doi: 10.14348/molcells.202 1.0211. PMID: 35289305; PMCID: PMC9095508.
17. Xin Qin, Jing Wang, Xing Wang, Tao Huang, Zhiqing Fang, Lei Yan, Yidong Fan, Dawei Xu, Widespread genomic/molecular alterations of DNA helicases and their clinical/therapeutic implications across human cancer, Biomedicine & Pharmacotherapy, Volume 158, 2023,114193, ISSN 0753-3322, https://doi.org/10.1016/j.biopha.2022.114193
18. Uchiumi F, Seki M, Furuichi Y. Helicases and human diseases. Front Genet. 2015 Feb 12;6:39. doi: 10.3389/fgene.2015.00039. PMID: 25729389; PMCID: PMC4325929
19. Upadhya S, Klein JA, Nathanson A, Holton KM, Barrett LE. Single-cell analyses reveal increased gene expression variability in human neurodevelopmental conditions. Am J Hum Genet. 2025 Apr 3;112(4): 876-891. doi: 10.1016/j.ajhg.2025.02.011. Epub 2025 Mar 7. PMID: 40056913; PMCID: PMC12081229
20. Sun Young Moon, Yi Zheng, Rho GTPase-activating proteins in cell regulation, Trends in Cell Biology, Volume 13, Issue 1, 2003, Pages 13-22, ISSN 0962-8924, https://doi.org/10.1016/S0962-8924(02)00004-1
21. Clover, L.M., Sargent, I.L., Townsend, A., Tampé, R. and Redman, C.W.G. (1995), Expression of TAP1 by human trophoblast. Eur. J. Immunol., 25: 543-548. https://doi.org/10.1002/eji.1830250236
22. Wang Z-D, Tian X, Wang Y, Wang J-J, Ye S-Q, Huang Y-Q, Qu Y-Y, Chang K, Shi G-H, Ye D-W and Gu C-Y (2022) The expression and prognostic value of transporter 1, ATP binding cassette subfamily B member in clear cell renal cell cancer with experimental validation. Front. Oncol. 12:1013790. doi: 10.3389/fonc.2022.1013790
23. Crisler WJ, Eshleman EM, Lenz LL. Ligand-induced IFNGR1 down-regulation calibrates myeloid cell IFNγ responsiveness. Life Sci Alliance. 2019 Oct 4;2(5):e201900447. doi: 10.26508/lsa.201900447. PMID: 31585982 PMCID: PMC6778285).
24. Hom, B., Boyd, N.K., Vogel, B.N. et al. Down Syndrome and Autoimmune Disease. Clinic Rev Allerg Immunol 66, 261–273 (2024). https://doi.org/10.1007/s12016-024-08996-2
25. Xian S, Dosset M, Almanza G, Searles S, Sahani P, Waller TC, Jepsen K, Carter H, Zanetti M. The unfolded protein response links tumor aneuploidy to local immune dysregulation. EMBO Rep. 2021 Dec 6;22(12):e52509. doi: 10.15252/embr.202152509. Epub 2021 Oct 26. PMID: 34698427; PMCID: PMC8647024.
26. Choi Y, Seo H, Han J, Yoo I, Kim J, Ka H. Chemokine (C-C motif) Ligand 28 and Its Receptor CCR10: Expression and Function at the Maternal-Conceptus Interface in Pigs. Biol Reprod. 2016 Oct 1;95(4):84. doi: 10.1095/biolreprod.116.141903. Epub 2016 Aug 31. PMID: 27580990.
27. Pan JH, Zhou H, Cooper L, Huang JL, Zhu SB, Zhao XX, Ding H, Pan YL, Rong L. LAYN Is a Prognostic Biomarker and Correlated With Immune Infiltrates in Gastric and Colon Cancers. Front Immunol. 2019 Jan 29;10:6. doi: 10.3389/fimmu.2019.00006. PMID: 30761122; PMCID: PMC6362421.
28. Sánchez C, Díaz-Nido J, Avila J. Phosphorylation of microtubule-associated protein 2 (MAP2) and its relevance for the regulation of the neuronal cytoskeleton function. Prog Neurobiol. 2000 Jun;61 (2):133-68. doi: 10.1016/s0301-0082(99)00046-5. PMID: 10704996.
29. Bulinski JC, McGraw TE, Gruber D, Nguyen HL, Sheetz MP. Overexpression of MAP4 inhibits organelle motility and trafficking in vivo. J Cell Sci. 1997 Dec; 110 ( Pt 24):3055-64. doi: 10.1242/jcs.110.24.3055. PMID: 9365275.
30. Alasmari F, Ahmad A, Alsanea S, Hammad AM, Al-Qerem W. Current insights and prospects for the pathogenesis and treatment of clinical manifestations associated with Down syndrome through neurotransmitter, inflammatory, and oxidative stress pathways. Front Pharmacol. 2025 Apr 28;16:15922 77. doi: 10.3389/fphar.2025.1592277. PMID: 4035 6974; PMCID: PMC12066560.
31. Gulesserian, T., Engidawork, E., Cairns, N., & Lubec, G. (2000). Increased protein levels of serotonin transporter in frontal cortex of patients with Down syndrome. Neuroscience letters, 296(1), 53-57.
32. Sahni J, Nelson B, Scharenberg AM. SLC41A2 encodes a plasma-membrane Mg2+ transporter. Biochem J. 2007 Jan 15;401(2):505-13. doi: 10.104 2/BJ20060673. PMID: 16984228; PMCID: PMC182 0800.
33. Liu H, Zheng J, Liao A. The regulation and potential roles of m6A modifications in early embryonic development and immune tolerance at the maternal-fetal interface. Front Immunol. 2022 Sep 26;13:988130. doi: 10.3389/fimmu.2022.988130. PMID: 36225914; PMCID: PMC9549360.
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