Abstract
Miscarriages are one of the most common problems of pregnancy abnormalities, however, in most cases the etiology of this pathology is unknown. Herein, we applied differential scanning calorimetry to study the aging process of red blood cells (RBCs) derived from women with miscarriages as compared to healthy non-pregnant and pregnant women of reproductive age, with the aim to identify specific calorimetric features associated with high-risk pregnancy. The calorimetric profiles of RBCs derived from healthy pregnant and non-pregnant women along the cells aging path are characterized with: (1) slow reduction in the hemoglobin heat capacity and (2) downshift of the thermal transitions of hemoglobin, Band 3 and Band 2.1, 4.1 and 4.2 proteins. A large population (71%) of the studied cases with miscarriage are associated with faster aging of RBCs, i.e., faster thermal destabilization of hemoglobin and Band 3 transitions compared to healthy non-pregnant and pregnant women. The results suggest that the accelerated temperature-induced destabilization of RBCs from the majority of women that underwent miscarriages along cells aging is an additional criterion for estimation of the risk of miscarriage.
Similar content being viewed by others
References
Romero ST, Geiersbach KB, Paxton CN, Rose NC, Schisterman EF, Branch DW, Silver RM. Differentiation of genetic abnormalities in early pregnancy loss. Ultrasound Obstet Gynecol. 2015;45(1):89–94.
Giakoumelou S, Wheelhouse N, Cuschieri K, Entrican G, Howie SEM, Horne AW. The role of infection in miscarriage. Hum Reprod Update. 2016;22(1):116–33.
Kaur R, Gupta K. Endocrine dysfunction and recurrent spontaneous abortion: an overview. Int J Appl Basic Med Res. 2016;6(2):79–83.
Weisel JW, Litvinov RI. Red blood cells: the forgotten player in hemostasis and thrombosis. J Thromb Haemost. 2019;17(2):271–82.
Litvinov RI, Weisel JW. Role of red blood cells in haemostasis and thrombosis. ISBT Sci Ser. 2017;12(1):176–83.
Gersh KC, Nagaswami C, Weisel JW. Fibrin network structure and clot mechanical properties are altered by incorporation of erythrocytes. Tromb Heamost. 2009;102:1169–75.
Helms CC, Marvel M, Zhao W, Stahle M, Vest R, Kato GJ, Lee JS, Christ G, Gladwin MT, Hantgan RR, Kim-Shapiro DB. Mechanisms of hemolysis-associated platelet activation. J Thromb Haemost. 2013;11:2148–54.
Wang C, Lin L, Su R, Zhu W, Wei Y, Yan J, Feng H, Li B, Li S, Yang H. Hemoglobin levels during the first trimester of pregnancy are associated with the risk of gestational diabetes mellitus, pre-eclampsia and preterm birth in Chinese women: a retrospective study. BMC Pregnancy Childbirth. 2018;18(1):263.
Kadry S, Sleem C, Samad RA. Hemoglobin levels in pregnant women and its outcomes. Biom Biostat Int J. 2018;7(4):326–36.
Khoigani MG, Goli S, Hasanzadeh A. The relationship of hemoglobin and hematocrit in the first and second half of pregnancy with pregnancy outcome. Iran J Nurs Midwifery Res. 2012;17(2 Suppl 1):165–70.
Mutua DN, Njagi ENM, Orinda GO. Hematological profile of normal pregnant women. J Blood Lymph. 2018;8(2):1–6. https://doi.org/10.4172/2165-7831.1000220.
Belo L, Rebelo I, Castro EM, Catarino C, Pereira-Leite L, Quintanilha A, Santos-Silva A. Band 3 as a marker of erythrocyte changes in pregnancy. Eur J Haematol. 2002;69(3):145–51.
Garbett NC, Mekmaysy CS, DeLeeuw L, Chaires JB. Clinical application of plasma thermograms. Utility, practical approaches and considerations. Methods. 2015;76:41–50.
Todinova S, Krumova S, Kurtev P, Dimitrov V, Djongov L, Dudunkov Z, Taneva SG. Calorimetry-based profiling of blood plasma from colorectal cancer patients. J Biochim Biophys Acta Gen Subj. 2012;1820:1879–85.
Wiegand N, Bucs G, Dande A, Lorinczy D. Investigation of protein content of synovial fluids with DSC in different arthritides. J Therm Anal Calorim. 2019. https://doi.org/10.1007/s10973-019-08151-6.
Todinova SJ, Stoyanova E, Krumova SB, Iliev I, Taneva SG. Calorimetric signatures of human cancer cells and their nuclei. J Thermochim Acta. 2016;623:95–101.
Wilhelm F, Kovács KA, Vértes ZS, Lorinczy DL. Human uterus in pregnancy, as it can be monitored by DSC examination. J Therm Anal Calorim. 2007;89(3):863–5.
Dinarelli S, Longo G, Krumova S, Todinova S, Danailova A, Taneva SG, Lenzi E, Mussi V, Girasole M. Insights into the morphological pattern of erythrocytes’ aging: coupling quantitative AFM data to microcalorimetry and Raman spectroscopy. J Mol Recognit. 2018;31(11):e2732. https://doi.org/10.1002/jmr.2732.
Girasole M, Pompeo G, Cricenti A, Longo G, Boumis G, Bellelli A, Amiconi S. The how, when, and why of the aging signals appearing on the human erythrocyte membrane: an atomic force microscopy study of surface roughness. Nanomedicine. 2010;6(6):760–8. https://doi.org/10.1016/j.nano.2010.06.004.
Gaetano J. Welch‘s t-test for comparing two independent groups: an excel calculator (1.0.1) (2019).
Lepock JR. Measurement of protein stability and protein denaturation in cells using differential scanning calorimetry. Methods (San Diego, Calif). 2005;35(2):117–25.
Sakota D, Sakamoto R, Sobajima H, Yokoyama N, Waguri S, Ohuchi K, Takatani S. Mechanical damage of red blood cells by rotary blood pumps: selective destruction of aged red blood cells and subhemolytic trauma. Artif Organs. 2008;32:785–91.
Bosch FH, Werre JM, Schipper L, Roerdinkholder-Stoelwinder B, Huls T, Willekens FL, Wichers G, Halie MR. Determinants of red blood cell deformability in relation to cell age. Eur J Haematol. 1994;52:35–41.
Lutz HU, Bogdanova A. Mechanisms tagging senescent red blood cells for clearance in healthy humans. Front Physiol. 2013;4:387. https://doi.org/10.3389/fphys.2013.00387.
Rifkind JM, Nagababu E. Hemoglobin redox reactions and red blood cell aging. Antioxid Redox Signal. 2013;18:2274–83.
Lapshina EA, Zavodnik IB, Ignatenko VA. Thermal stability and functional properties of human hemoglobin in the presence of aliphatic alcohols. Mol Biol. 1992;26:315–20.
Michnik A, Drzazga Z, Kluczewska A. Differential scanning microcalorimetry study of the thermal denaturation of haemoglobin. Biophys Chem. 2005;118:93–101.
Shaklai N, Frayman B, Fortier N, Snyder M. Crosslinking of isolated cytoskeletal proteins with hemoglobin: a possible damage inflicted to the red cell membrane. Biochim Biophys Acta. 1987;915:406–14.
Snyder LM, Fortier NL, Trainor J, Jacobs J, Leb L, Lubin B, Chiu D, Shohet S, Mohandas N. Effect of hydrogen peroxide exposure on normal human-erythrocyte deformability, morphology, surface characteristics and spectrin–hemoglobin cross-linking. J Clin Invest. 1985;76:1971–7.
Torkzahrani S, Ataei PJ, Hedayati M, Khodakarim S, Sheikhan Z, Khoramabadi M, Sadraei A. Oxidative stress markers in early pregnancy loss: a case-control study. Int J Women’s Health Reprod Sci. 2019;7(1):61–6.
Low PS. Role of hemoglobin denaturation and band 3 clustering in initiating red cell removal. In: Magnani M, De Flora A, editors. Red blood cell aging. advances in experimental medicine and biology. Boston: Springer; 1991. p. 307.
Bosman GJ, Stappers M, Novotný VM. Changes in band 3 structure as determinants of erythrocyte integrity during storage and survival after transfusion. Blood Transfus. 2010;8(Suppl 3):s48–52. https://doi.org/10.2450/2010.008S.
Pajić-Lijaković I, Milivojevic M. Role of band 3 in the erythrocyte membrane structural changes under isotonic and hypotonic conditions. In: Jimenez-Lopez JC, editor. Cytoskeleton: structure, dynamics, function and disease. Norderstedt: BoD–Books on Demand; 2017.
Mohanty JG, Nagababu E, Rifkind JM. Red blood cell oxidative stress impairs oxygen delivery and induces red blood cell aging. Front Physiol. 2014;5:84. https://doi.org/10.3389/fphys.2014.00084.
Badior KE, Casey JR. Molecular mechanism for the red blood cell senescence clock. IUBMB Life. 2018;70(1):32–40. https://doi.org/10.1002/iub.1703.
Akoev VR, Matveev AV, Belyaeva TV, Kim YA. The effect of oxidative stress on structural transitions of human erythrocyte ghost membranes. Biochim Biophys Acta. 1998;1371:284–94.
Rybicki AC, Heath R, Wolf JL, Lubin B, Schwartz RS. Deficiency of protein 4.2 in erythrocytes from a patient with a Coombs negative hemolytic anemia. J Clin Invest. 1988;81:893–901.
Acknowledgements
This work is supported by Grant КП-06-H21/4, competition for financial support for basic research projects—2018, Bulgarian National Science Fund.
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Langari, A., Danailova, A., Krumova, S. et al. Aging-related changes in the calorimetric profile of red blood cells from women with miscarriages. J Therm Anal Calorim 142, 1919–1926 (2020). https://doi.org/10.1007/s10973-020-10112-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10973-020-10112-3