Proteomics of the Human First Trimester Chorionic Villi Associated with Anembryonic Pregnancy
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Abstract
In this study, the proteomic approach based on high performance liquid chromatography connected with tandem mass spectrometry (LC-MS/MS) and bioinformatics analysis were applied to identify differentially abundant proteins in chorionic villus samples (CVS) from women with blighted ovum and normal pregnancy. We identified about 600 proteins in the solubilized fraction of CVS. Comparative proteomic analysis revealed differences in the content (Average Normalized Abundances) of 187 proteins in blighted ovum. These included 134 down-regulated proteins and 53 up-regulated proteins. According to bioinformatics analysis these proteins participate in a variety of metabolic processes, including alcohol and tricarboxylic acid metabolism, response to endoplasmic reticulum stress, small molecular catabolic process, cellular respiration, and others. Proteins that demonstrated growing content in blighted ovum were mainly encoded by genes located on chromosomes 7 and 16 whereas proteins which demonstrated reducing abundance were mainly encoded by genes located on chromosomes 1, 2, and 11. We also revealed changes in the content of proteins encoded by genes located on the human chromosome 18; they are involved in apoptotic and drug metabolic processes with an important role in early pregnancy loss. Our pilot results demonstrate the efficiency of the LC-MS/MS approach for detecting the differences at the qualitative and semi-quantitative levels in the protein profiles of the CVS at anembryonic pregnancy compared to normal gestation. We conclude that globally profiled and differentially regulated proteins of CVS are helpful in obtaining molecular insights into biological processes of the pregnancy pathology.
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References
- Carlson, L.M., & Vora, N.L. (2017). Prenatal Diagnosis: Screening and Diagnostic Tools. Obstet Gynecol Clin North Am., 44(2), 245-256. DOI
- Badeau, M., Lindsay, C., Blais, J., Nshimyumukiza, L., Takwoingi, Y., Langlois, S., Légaré, F., Giguère, Y., Turgeon, A.F., Witteman, W., & Rousseau, F. (2017). Genomics-based non-invasive prenatal testing for detection of fetal chromosomal aneuploidy in pregnant women. Cochrane Database Syst Rev., 11, CD011767. DOI
- Petushkova, N.A. (1991). First-trimester diagnosis of an unusual case of alpha-mannosidosis. Prenat Diagn., 11(5) 279-283. DOI
- Verma, J., Bijarnia-Mahay, S., & Verma, I.C. (2017). Prenatal Diagnosis of Lysosomal Storage Disorders Using Chorionic Villi. Methods Mol Biol., 159(4), 265-291. DOI
- Sun, Y.V., & Hu, Y.J. (2016). Integrative Analysis of Multi-omics Data for Discovery and Functional Studies of Complex Human Diseases. Adv Genet., 93, 147-190. DOI
- Liu, A.X., Jin, F., Zhang, W.W., Zhou, T.H., Zhou, C.Y., Yao, W.M., Qian. Y.L. , & Huang, H.F. (2006). Proteomic analysis on the alteration of protein expression in the placental villous tissue of early pregnancy loss. Biol Reprod., 75(3), 414-420. DOI
- Ni, X., Li, X., Guo, Y., Zhou. T., Guo, X., Zhao, C., Lin, M., Zhou, Z., Shen, R., Guo, X., Ling, X., & Huo, R. (2014). Quantitative proteomics analysis of altered protein expression in the placental villous tissue of early pregnancy loss using isobaric tandem mass tags. Biomed Res Int., 647143. DOI
- Kedia, K., Nichols, C.A., Thulin, C.D., & Graves, S.W. (2015). Novel "omics" approach for study of low-abundance, low-molecular-weight components of a complex biological tissue: regional differences between chorionic and basal plates of the human placenta. Anal Bioanal Chem., 407(28), 8543-8556. DOI
- Xanthopoulou, A.G., Anagnostopoulos, A.K., Thanasopoulou, A., Anastasiadou, E., Sifakis, S., Siafaka-Kapadai, A., & Tsangaris, G.T. (2011). The proteome of normal human chorionic villus sampling cells. In Vivo, 25(6), 945-961. DOI
- Luo, Q., Jiang, Y., Jin, M., Xu, J., & Huang, H.F. (2013). Proteomic analysis on the alteration of protein expression in the early-stage placental villous tissue of electromagnetic fields associated with cell phone exposure. Reprod Sci., 20(9), 1055-1061. DOI
- Xin, L., Xu, B., Ma, L., Hou, Q., Ye, M., Meng, S., Ding, X., & Ge, W. (2016). Proteomics study reveals that the dysregulation of focal adhesion and ribosome contribute to early pregnancy loss. Proteomics Clin Appl., 10(5), 554-563. DOI
- Fujikura, T., Froehlich, L.A., & Driscoll, S.G. (1966). A simplified anatomic classification of abortions. Am J Obstet Gynecol., 95(7), 902-905. DOI
- Chen, H.F., Chao, K.H., Shew, J.Y., Yang, Y.S., & Ho, H.N. (2004). Expression of leukemia inhibitory factor and its receptor is not altered in the decidua and chorionic villi of human anembryonic pregnancy. Hum Reprod., 19(7), 1647-1654. DOI
- Bradford, M. M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem, 72, 248–254. DOI
- Rodchenkova, M., & Novikova, S. (2013). Optimization of liquid chromatography with mass spectrometric detection method for the qualitative and semi-quantitative proteomic analysis. Analitika, 3(10), 40-47.
- Petushkova, N.A., Zgoda, V.G., Pyatnitskiy, M.A., Larina, O.V., Teryaeva, N.B., Potapov, A.A., & Lisitsa, A.V. (2017). Post-translational modifications of FDA-approved plasma biomarkers in glioblastoma samples. PLoS One, 12(5), e0177427. DOI
- Elias, J. E., & Gygi, S.P. (2007). Target-decoy search strategy for increased confidence in large-scale protein identifications by mass spectrometry. Nat. Methods, 4, 207–214. DOI
- Yu, G., Wang, L.G., Han, Y., & He, Q.Y. (2012). ClusterProfiler: an R package for comparing biological themes among gene clusters. OMICS, 16(5), 284-287. DOI
- Demko, Z.P., Simon, A.L., McCoy, R.C., Petrov, D.A., & Rabinowitz, M. (2016). Effects of maternal age on euploidy rates in a large cohort of embryos analyzed with 24-chromosome single-nucleotide polymorphism-based preimplantation genetic screening. Fertil Steril, 105(5), 1307 – 1313. DOI
- Blaschitz, A., Weiss, U., Dohr, G., & Desoye, G. (2000). Antibody reaction patterns in first trimester placenta: implications for trophoblast isolation and purity screening. Placenta, 21, 733–741. DOI
- Heng, S., Cervero, A., Simon, C., Stephens, A.N., Li, Y., Zhang, J. Paule, S., Rainczuk, A., Singh, H., Quinonero, A., Tapia, A., Velasquez, L., Salamonsen, L., Rombauts, L.J. , & Nie, G. (2011). Proprotein convertase 5/6 is critical for embryo implantation in women: regulating receptivity by cleaving EBP50, modulating ezrin binding, and membrane-cytoskeletal interactions. Endocrinology, 152, 5041–5052. DOI
- Yamada, K.D., Omori, S., Nishi, H., & Miyagi, M. (2017). Identification of the sequence determinants of protein N-terminal acetylation through a decision tree approach. BMC Bioinformatics, 18(1), 289. DOI
- Cao, W., Liu, N., Tang, S., Bao, L., Shen, L., Yuan, H., Zhao, X., & Lu, H. (2008). Acetyl-Coenzyme A acyltransferase 2 attenuates the apoptotic effects of BNIP3 in two human cell lines. Biochim Biophys Acta, 1780(6), 873-880. DOI
- Ryu, S.J., & Park, S.C. (2009). Targeting major vault protein in senescence-associated apoptosis resistance. Expert Opin Ther Targets, 13(4), 479-484. DOI
- Hargreaves, G.A., Quinn, H., Kashem, M.A., Matsumoto, I., & McGregor, I.S. (2009). Proteomic analysis demonstrates adolescent vulnerability to lasting hippocampal changes following chronic alcohol consumption. Alcohol Clin Exp Res., 33(1), 86-94. DOI
- Zou, Y., Yu, X., Lu, J., Jiang, Z., Zuo, Q., Fan, M., Huang, S., & Sun, L. (2015). Decorin-Mediated Inhibition of Human Trophoblast Cells Proliferation, Migration, and Invasion and Promotion of Apoptosis In Vitro. Biomed Res Int., 2015, 201629. DOI
- Kokkinos, M.I. (2009). A novel role for ac-FOX-O1 in fetal membrane rupture. Reprod Sci., 16(7), 625 - 626. DOI
- Jadhav, A.A., & Jain, A. (2013). Adenosine deaminase activity in normal pregnancy and pregnancy associated disorders. Arch Physiol Biochem., 119(2), 88 – 91. DOI
- Varland, S., Osberg, C., & Arnesen, T. (2015). N-terminal modifications of cellular proteins: The enzymes involved, their substrate specificities and biological effects. Proteomics, 15(14), 2385 - 2401. DOI