Placenta-mediated complications: Nucleosomes and free DNA concentrations differ depending on subtypes

Sylvie Bouvier, Eve Mousty, Mathieu Fortier, Christophe Demattei, Eric Mercier, Eva Nouvellon, Mathias Chea, Frédéric Grosjean, Vincent Letouzey, Jean-Christophe Gris, Sylvie Bouvier, Eve Mousty, Mathieu Fortier, Christophe Demattei, Eric Mercier, Eva Nouvellon, Mathias Chea, Frédéric Grosjean, Vincent Letouzey, Jean-Christophe Gris

Abstract

Background: Placenta-mediated pregnancy complications generate short- and long-term adverse medical outcomes for both the mother and the fetus. Nucleosomes and free DNA (fDNA) have been described in patients suffering from a wide range of inflammatory conditions.

Objective: The objective of our study was to compare nucleosomes and fDNA circulating levels during pregnancy and particularly in women developing a placenta-mediated complication according to the subtype (preeclampsia or intrauterine growth restriction) (NCT01736826).

Patients/methods: A total of 115 women were prospectively included in the study across three groups: 30 healthy non-pregnant women, 50 with normal pregnancy, and 35 with a complicated pregnancy. Blood samples were taken up to every 4 weeks for several women with normal pregnancy and nucleosomes and fDNA were quantified using enzyme-linked immunosorbent assay and quantitative polymerase chain reaction, respectively.

Results: We show that nucleosomes and fDNA concentrations significantly increase during normal pregnancy, with concentrations at delivery differing between the two groups. Interestingly, we show that concentrations differ according to the type of placenta-mediated complications, with higher levels in preeclampsia compared to intrauterine growth restriction.

Conclusions: These data suggest that nucleosomes and fDNA may be additional actors participating in placenta-mediated pregnancy complications.

Keywords: cell-free DNA; hyper-coagulability; intrauterine growth restriction; nucleosomes; preeclampsia; pregnancy.

© 2020 International Society on Thrombosis and Haemostasis.

References

REFERENCES

    1. Lane-Cordova AD, Khan SS, Grobman WA, Greenland P, Shah SJ. Long-Term Cardiovascular Risks Associated With Adverse Pregnancy Outcomes: JACC Review Topic of the Week. J Am Coll Cardiol. 2019;73:2106-2116.
    1. Sattar N, Greer IA. Pregnancy complications and maternal cardiovascular risk: opportunities for intervention and screening? BMJ. 2002;325:157-160.
    1. Pepine CJ, Anderson RD, Sharaf BL, et al. Coronary microvascular reactivity to adenosine predicts adverse outcome in women evaluated for suspected ischemia results from the National Heart, Lung and Blood Institute WISE (women's ischemia syndrome evaluation) study. J Am Coll Cardiol. 2010;55:2825-2832.
    1. Bellamy L, Casas JP, Hingorani AD, Williams DJ. Preeclampsia and risk of cardiovascular disease and cancer in later life: Systematic review and meta-analysis. BMJ. 2007;335:974.
    1. Bokslag A, van Weissenbruch M, Mol BW, de Groot CJ. Preeclampsia; short and long-term consequences for mother and neonate. Early Hum Dev. 2016;102:47-50.
    1. Crispi F, Miranda J, Gratacós E. Long-term cardiovascular consequences of fetal growth restriction: biology, clinical implications, and opportunities for prevention of adult disease. Am J Obstet Gynecol. 2018;218:S869-S879.
    1. Report of the National High Blood Pressure Education Program. Working group report on high blood pressure in pregnancy. Am J Obstet Gynecol. 2000;183:S1-S22.
    1. Sibai B, Dekker G, Kupferminc M. Preeclampsia. Lancet. 2005;4(365):785-799.
    1. ACOG Practice Bulletin No. 202: Gestational Hypertension and Preeclampsia. Obstet Gynecol. 2019;133:e1-25.
    1. Khodzhaeva ZS, Kogan YA, Shmakov RG, et al. Clinical and pathogenetic features of early- and late-onset preeclampsia. J Matern Fetal Neonatal Med. 2016;29:2980-2986.
    1. Redman CW, Sargent IL. Latest advances in understanding preeclampsia. Science. 2005;10(308):1592-1594.
    1. Albu AR, Horhoianu IA, Dumitrascu MC, Horhoianu V. Growth assessment in diagnosis of Fetal Growth Restriction. Review. J Med Life. 2014;7:150-154.
    1. Burton GJ, Jauniaux E. Pathophysiology of placental-derived fetal growth restriction. Am J Obstet Gynecol. 2018;218:S745-S761.
    1. O'Gorman N, Wright D, Poon LC, et al. Multicenter screening for preeclampsia by maternal factors and biomarkers at 11-13 weeks' gestation: comparison with NICE guidelines and ACOG recommendations. Ultrasound Obstet Gynecol. 2017;49:756-760.
    1. Zeisler H, Hund M, Verlohren S. The sFlt-1:PlGF Ratio in Women with suspected preeclampsia. N Engl J Med. 2016;374:1785-1786.
    1. Huppertz B. An updated view on the origin and use of angiogenic biomarkers for preeclampsia. Expert Rev Mol Diagn. 2018;18:1-9.
    1. Massberg S, Grahl L, von Bruehl ML, et al. Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases. Nat Med. 2010;16:887-896.
    1. Aharon A, Brenner B. Microparticles and pregnancy complications. Thromb Res. 2011;127:S67-71.
    1. Kohli S, Ranjan S, Hoffmann J, et al. Maternal extracellular vesicles and platelets promote preeclampsia via inflammasome activation in trophoblasts. Blood. 2016;128:2153-2164.
    1. Brown MA, Magee LA, Kenny LC, et al. International Society for the Study of Hypertension in Pregnancy (ISSHP). The hypertensive disorders of pregnancy: ISSHP classification, diagnosis & management recommendations for international practice. Pregnancy Hypertens. 2018;13:291-310.
    1. Price CP, Newall RG, Boyd JC. Use of protein:creatinine ratio measurements on random urine samples for prediction of significant proteinuria: a systematic review. Clin Chem. 2005;51:1577-1586.
    1. Gordijn SJ, Beune IM, Thilaganathan B, et al. Consensus definition of fetal growth restriction: a Delphi procedure. Ultrasound Obstet Gynecol. 2016;48:333-339.
    1. Holdenrieder S, Stieber P. Clinical use of circulating nucleosomes. Crit Rev Clin Lab Sci. 2009;46:1-24.
    1. Holdenrieder S, Stieber P, Bodenmüller H, et al. Nucleosomes in serum as a marker for cell death. Clin Chem Lab Med. 2001;39:596-605.
    1. Holdenrieder S, Stieber P, Chan LY, et al. Cell-free DNA in serum and plasma: comparison of ELISA and quantitative PCR. Clin Chem. 2005;51:1544-1546.
    1. Granger V, Faille D, Marani V, et al. Human blood monocytes are able to form extracellular traps. J Leukoc Biol. 2017;102:775-781.
    1. Lo YM, Leung TN, Tein MSC, et al. Quantitative abnormalities of fetal DNA in maternal serum in preeclampsia. Clin Chem. 1999;45:184-188.
    1. Zhong XY, Holzgreve W, Hahn S. The levels of circulatory cell free fetal DNA in maternal plasma are elevated prior to the onset of preeclampsia. Hypertens Pregnancy. 2002;21:77-83.
    1. Zhong XY, Laivuori H, Livingston JC, et al. Elevation of both maternal and fetal extracellular circulating deoxyribonucleic acid concentrations in the plasma of pregnant women with preeclampsia. Am J Obstet Gynecol. 2001;184:414-419.
    1. Zhong XY, Gebhardt S, Hillermann R, Tofa KC, Holzgreve W, Hahn S. Circulatory nucleosome levels are significantly increased in early and late-onset preeclampsia. Prenat Diagn. 2005;25:700-703.
    1. Hu Y, Li H, Yan R, et al. Increased neutrophil activation and plasma DNA levels in patients with pre-eclampsia. Thromb Haemost. 2018;118(12):2064-2073.
    1. Rovere-Querini P, Castiglioni MT, Sabbadini MG, Manfredi AA. Signals of cell death and tissue turnover during physiological pregnancy, preeclampsia, and autoimmunity. Autoimmunity. 2007;40:290-294.
    1. Mitchell MD, Peiris HN, Kobayashi M, et al. Salomon C. Placental exosomes in normal and complicated pregnancy. Am J Obstet Gynecol. 2015;213:S173-181.
    1. Aharon A, Brenner B. Placenta-derived microparticles. Thromb Res. 2013;131:S22-24.
    1. Paules C, Youssef L, Rovira C, et al. Distinctive patterns of placental lesions in preeclampsia versus fetal growth restriction and their association with fetoplacental Doppler. Ultrasound Obstet Gynecol. 2019;54:609-616.
    1. Dudding T, Heron J, Thakkinstian A, et al. Factor V Leiden Is Associated With Pre-Eclampsia but Not With Fetal Growth Restriction: A Genetic Association Study and Meta-Analysis. J Thromb Haemost. 2008;6(11):1869-1875.

Source: PubMed

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