Reproductive Sciences

, Volume 19, Issue 6, pp 650–657 | Cite as

Plasma Clusterin Increased Prior to Small for Gestational Age (SGA) Associated With Preeclampsia and Decreased Prior to SGA in Normotensive Pregnancies

  • Marion BlumensteinEmail author
  • Lesley M. E. McCowan
  • Steven Wu
  • Garth J. S. Cooper
  • Robyn A. North
  • on behalf of the SCOPE consortium
Original Articles


In our search for early biomarkers for the pregnancy complicationssmall for gestational age (SGA) and preeclampsia (PE) we analysed plasma from 19-21 weeks gestation in women recruited into the SCOPE study, a prospective cohort of nulliparous women, by differential in gel electrophoresis (DIGE). DIGE revealed the differential expression of clusterin levels and its isoforms in top6-depleted plasma of women who delivered an SGA infant but remained normotensive (SGA-NT; N = 8) compared to healthy women with an uncomplicated pregnancy outcome (Controls, N = 8). Immunosorbent enzyme-linked assay (ELISA) showed that compared to plasma clusterin levels from healthy controls [71.1 (SD 12.4) µg/mL, n = 39], clusterin was decreased in SGA-NT [58.3 (SD 11.7), N = 20, P < 0.0001], increased in women with SGA and PE [81.5 (SD 14.8), N = 20, P < 0.01], but similar in PE alone [71.2 (SD 9.4)g/ml, P = 1.0]. Screening for clusterin levels and/or its different isoformsmay be useful in mid-pregnancy to identify women who subsequently develop SGA but remain normotensive or who develop preeclampsia with SGA.


difference in gel electrophoresis small for gestational age preeclampsia plasma clusterin DIGE 


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  1. 1.
    McCormick MC. The contribution of low birth weight to infant mortality and childhood morbidity. N Engl J Med. 1985;312(2): 82–90.CrossRefGoogle Scholar
  2. 2.
    McCowan LME, Roberts CT, Dekker GA, et al; SCOPE consortium. Risk factors for small-for-gestational-age infants by customized birthweight centiles: data from an international prospective cohort study. Br J Obstet Gynaecol. 2010;117(13): 1599–1607.CrossRefGoogle Scholar
  3. 3.
    Groom KM, North RA, Poppe KK, Sadler L, McCowan LM. The association between customized small for gestational age infants and pre-eclampsia or gestational hypertension varies with gestation at delivery. Br J Obstet Gynaecol. 2007;114(4): 478–484.CrossRefGoogle Scholar
  4. 4.
    Redman CW, Sargent IL. Latest advances in understanding preeclampsia. Science. 2005;308(5728): 1592–1594.CrossRefGoogle Scholar
  5. 5.
    Ness RB, Sibai BM. Shared and disparate components of the pathophysiologies of fetal growth restriction and preeclampsia. Am J Obstet Gynecol. 2006;195(1): 40–49.CrossRefGoogle Scholar
  6. 6.
    Shankar R, Gude N, Cullinane F, Brennecke S, Purcell AW, Moses EK. An emerging role for comprehensive proteome analysis in human pregnancy research. Reproduction. 2005;129(6): 685–696.CrossRefGoogle Scholar
  7. 7.
    Blumenstein M, McMaster MT, Black MA, et al. A proteomic approach identifies early pregnancy biomarkers for preeclampsia: novel linkages between a predisposition to preeclampsia and cardiovascular disease. Proteomics. 2009;9(11): 2929–2945.CrossRefGoogle Scholar
  8. 8.
    Watanabe H, Hamada H, Yamada N, et al. Proteome analysis reveals elevated serum levels of clusterin in patients with preeclampsia. Proteomics. 2004;4(2): 537–543.CrossRefGoogle Scholar
  9. 9.
    Blankley RT, Gaskell SJ, Whetton AD, Dive C, Baker PN, Myers JE. A proof-of-principle gel-free proteomics strategy for the identification of predictive biomarkers for the onset of pre-eclampsia. Br J Obstet Gynaecol. 2009;116(11): 1473–1480.CrossRefGoogle Scholar
  10. 10.
    Auer J, Camoin L, Guillonneau F, et al. Serum profile in preeclampsia and intra-uterine growth restriction revealed by iTRAQ technology. J Proteomics. 2010;73(5): 1004–1017.CrossRefGoogle Scholar
  11. 11.
    Jenne DE, Tschopp J. Clusterin: the intriguing guises of a widely expressed glycoprotein. Trends Biochem Sci. 1992;17(4): 154–159.CrossRefGoogle Scholar
  12. 12.
    McCowan L, North R, Taylor R. ACTRN12607000551493. Australian New Zealand Clinical Trials Registry, 2007.
  13. 13.
    Gardosi J, Mongelli M, Wilcox M, Chang A. An adjustable fetal weight standard. Ultrasound Obstet Gynecol. 1995;6(3): 168–174.CrossRefGoogle Scholar
  14. 14.
    North RA, McCowan LM, Dekker GA, et al. Clinical risk prediction for pre-eclampsia in nulliparous women: development of model in international prospective cohort. BMJ. 2011; 342: d1875.CrossRefGoogle Scholar
  15. 15.
    Shin JK, Han KA, Kang MY, et al. Expression of clusterin in normal and preeclamptic placentas. J Obstet Gynaecol Res. 2008;34(4): 473–479.CrossRefGoogle Scholar
  16. 16.
    Witte DP, Aronow BJ, Stauderman ML, et al. Platelet activation releases megakaryocyte-synthesized apolipoprotein J, a highly abundant protein in atheromatous lesions. Am J Pathol. 1993;143(3): 763–773.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Chen M, Yuan Z, Shan K. Association of apolipoprotein J gene 866C–>T polymorphism with preeclampsia and essential hypertension. Gynecol Obstet Invest. 2005;60(3): 133–138.CrossRefGoogle Scholar
  18. 18.
    Bartl MM, Luckenbach T, Bergner O, Ullrich O, Koch-Brandt C. Multiple receptors mediate apoJ-dependent clearance of cellular debris into nonprofessional phagocytes. Exp Cell Res. 2001;271(1): 130–141.CrossRefGoogle Scholar
  19. 19.
    Santilli G, Aronow BJ, Sala A. Essential requirement of apolipoprotein J (clusterin) signaling for IkappaB expression and regulation of NF-kappaB activity. J Biol Chem. 2003;278(40): 38214–38219.CrossRefGoogle Scholar
  20. 20.
    Schwarz M, Spath L, Lux CA, et al. Potential protective role of apoprotein J (clusterin) in atherogenesis: binding to enzymatically modified low-density lipoprotein reduces fatty acid-mediated cytotoxicity. Thromb Haemost. 2008;100(1): 110–118.PubMedGoogle Scholar
  21. 21.
    Sivamurthy N, Stone DH, Logerfo FW, Quist WC. Apolipoprotein J inhibits the migration, adhesion, and proliferation of vascular smooth muscle cells. J Vasc Surg. 2001;34(4): 716–723.CrossRefGoogle Scholar
  22. 22.
    Trougakos IP, Djeu JY, Gonos ES, Boothman DA. Advances and challenges in basic and translational research on clusterin. Cancer Res. 2009;69(2): 403–406.CrossRefGoogle Scholar
  23. 23.
    Kapron JT, Hilliard GM, Lakins JN, et al. Identification and characterization of glycosylation sites in human serum clusterin. Protein Sci. 1997;6(10): 2120–2133.CrossRefGoogle Scholar
  24. 24.
    Cochrane DR, Wang Z, Muramaki M, Gleave ME, Nelson CC. Differential regulation of clusterin and its isoforms by androgens in prostate cells. J Biol Chem. 2007;282(4): 2278–2287.CrossRefGoogle Scholar
  25. 25.
    Hellebrekers DM, Melotte V, Vire E, et al. Identification of epigenetically silenced genes in tumor endothelial cells. Cancer Res. 2007;67(9): 4138–4148.CrossRefGoogle Scholar
  26. 26.
    Jackson JK, Gleave ME, Gleave J, Burt HM. The inhibition of angiogenesis by antisense oligonucleotides to clusterin. Angiogenesis. 2005;8(3): 229–238.CrossRefGoogle Scholar
  27. 27.
    Stewart EM, Aquilina JA, Easterbrook-Smith SB, et al. Effects of glycosylation on the structure and function of the extracellular chaperone clusterin. Biochemistry. 2007;46(5): 1412–1422.CrossRefGoogle Scholar
  28. 28.
    Arkwright PD, Redman CW, Williams PJ, Dwek RA, Rademacher TW. Syncytiotrophoblast membrane protein glycosylation patterns in normal human pregnancy and changes with gestational age and parturition. Placenta. 1991;12(6): 637–651.CrossRefGoogle Scholar
  29. 29.
    Karamessinis PM, Malamitsi-Puchner A, Boutsikou T, et al. Marked defects in the expression and glycosylation of alpha2-HS glycoprotein/fetuin-A in plasma from neonates with intrauterine growth restriction: proteomics screening and potential clinical implications. Mol Cell Proteomics. 2008;7(3): 591–599.CrossRefGoogle Scholar
  30. 30.
    Rodriguez-Pineiro AM, de la Cadena MP, Lopez-Saco A, Rodriguez-Berrocal FJ. Differential expression of serum clusterin isoforms in colorectal cancer. Mol Cell Proteomics. 2006;5(9): 1647–1657.CrossRefGoogle Scholar

Copyright information

© Society for Reproductive Investigation 2012

Authors and Affiliations

  • Marion Blumenstein
    • 1
    • 6
    Email author
  • Lesley M. E. McCowan
    • 2
  • Steven Wu
    • 1
  • Garth J. S. Cooper
    • 1
    • 3
    • 4
  • Robyn A. North
    • 2
    • 5
  • on behalf of the SCOPE consortium
  1. 1.School of Biological Sciences, Faculty of ScienceUniversity of AucklandAucklandNew Zealand
  2. 2.Department of Obstetrics & Gynecology, Faculty of Medical & Health SciencesUniversity of AucklandAucklandNew Zealand
  3. 3.Centre for Advanced Discovery and Experimental Therapeutics (CADET), School of BiomedicineThe University of Manchester, Central Manchester University Hospitals NHS Foundation TrustManchesterUK
  4. 4.Maurice Wilkins Centre for Biodiscovery, Faculty of ScienceUniversity of AucklandAucklandNew Zealand
  5. 5.Division of Women’s HealthKing’s College LondonUK
  6. 6.University of Auckland, Kate Edger Information CommonsAucklandNew Zealand

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