Virchows Archiv

, Volume 453, Issue 4, pp 387–400

Placental protein 13 (galectin-13) has decreased placental expression but increased shedding and maternal serum concentrations in patients presenting with preterm pre-eclampsia and HELLP syndrome

  • Nandor Gabor Than
  • Omar Abdul Rahman
  • Rita Magenheim
  • Balint Nagy
  • Tibor Fule
  • Beata Hargitai
  • Marei Sammar
  • Petronella Hupuczi
  • Adi L. Tarca
  • Gabor Szabo
  • Ilona Kovalszky
  • Hamutal Meiri
  • Istvan Sziller
  • Janos Rigo Jr.
  • Roberto Romero
  • Zoltan Papp
Original Article

Abstract

Placental protein 13 (PP13) is a galectin expressed by the syncytiotrophoblast. Women who subsequently develop preterm pre-eclampsia have low first trimester maternal serum PP13 concentrations. This study revealed that third trimester maternal serum PP13 concentration increased with gestational age in normal pregnancies (p < 0.0001), and it was significantly higher in women presenting with preterm pre-eclampsia (p = 0.02) and hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome (p = 0.01) than in preterm controls. Conversely, placental PP13 mRNA (p = 0.03) and protein, as well as cytoplasmic PP13 staining of the syncytiotrophoblast (p < 0.05) was decreased in these pathological pregnancies compared to controls. No differences in placental expression and serum concentrations of PP13 were found at term between patients with pre-eclampsia and control women. In contrast, the immunoreactivity of the syncytiotrophoblast microvillous membrane was stronger in both term and preterm pre-eclampsia and HELLP syndrome than in controls. Moreover, large syncytial cytoplasm protrusions, membrane blebs and shed microparticles strongly stained for PP13 in pre-eclampsia and HELLP syndrome. In conclusion, parallel to its decreased placental expression, an augmented membrane shedding of PP13 contributes to the increased third trimester maternal serum PP13 concentrations in women with preterm pre-eclampsia and HELLP syndrome.

Keywords

Brush border membrane Galectin Syncytiotrophoblast microparticle Trafficking Virtual microscopy 

References

  1. 1.
    Myatt L (2002) Role of placenta in preeclampsia. Endocrine 19:103–111PubMedCrossRefGoogle Scholar
  2. 2.
    Sibai B, Dekker G, Kupferminc M (2005) Pre-eclampsia. Lancet 365:785–799PubMedGoogle Scholar
  3. 3.
    Lyall F (2005) Priming and remodelling of human placental bed spiral arteries during pregnancy—a review. Placenta 26(Suppl A):S31–S36PubMedCrossRefGoogle Scholar
  4. 4.
    Espinoza J, Romero R, Mee KY et al (2006) Normal and abnormal transformation of the spiral arteries during pregnancy. J Perinat Med 34:447–458PubMedCrossRefGoogle Scholar
  5. 5.
    Torry DS, Wang HS, Wang TH et al (1998) Preeclampsia is associated with reduced serum levels of placenta growth factor. Am J Obstet Gynecol 179:1539–1544PubMedCrossRefGoogle Scholar
  6. 6.
    Maynard SE, Min JY, Merchan J et al (2003) Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest 111:649–658PubMedGoogle Scholar
  7. 7.
    Chaiworapongsa T, Romero R, Espinoza J et al (2004) Evidence supporting a role for blockade of the vascular endothelial growth factor system in the pathophysiology of preeclampsia. Young Investigator Award. Am J Obstet Gynecol 190:1541–1547PubMedCrossRefGoogle Scholar
  8. 8.
    Venkatesha S, Toporsian M, Lam C et al (2006) Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat Med 12:642–649PubMedCrossRefGoogle Scholar
  9. 9.
    Roberts JM, Taylor RN, Musci TJ et al (1989) Preeclampsia: an endothelial cell disorder. Am J Obstet Gynecol 161:1200–1204PubMedGoogle Scholar
  10. 10.
    Redman CW, Sacks GP, Sargent IL (1999) Preeclampsia: an excessive maternal inflammatory response to pregnancy. Am J Obstet Gynecol 180:499–506PubMedCrossRefGoogle Scholar
  11. 11.
    Gervasi MT, Chaiworapongsa T, Pacora P et al (2001) Phenotypic and metabolic characteristics of monocytes and granulocytes in preeclampsia. Am J Obstet Gynecol 185:792–797PubMedCrossRefGoogle Scholar
  12. 12.
    Jauniaux E, Poston L, Burton GJ (2006) Placental-related diseases of pregnancy: involvement of oxidative stress and implications in human evolution. Hum Reprod Updat 12:747–755CrossRefGoogle Scholar
  13. 13.
    Myatt L, Miodovnik M (1999) Prediction of preeclampsia. Semin Perinatol 23:45–57PubMedCrossRefGoogle Scholar
  14. 14.
    von Dadelszen P, Magee LA, Roberts JM (2003) Subclassification of preeclampsia. Hypertens Pregnancy 22:143–148CrossRefGoogle Scholar
  15. 15.
    Moldenhauer JS, Stanek J, Warshak C et al (2003) The frequency and severity of placental findings in women with preeclampsia are gestational age dependent. Am J Obstet Gynecol 189:1173–1177PubMedCrossRefGoogle Scholar
  16. 16.
    Redman CW, Sargent IL (2005) Latest advances in understanding preeclampsia. Science 308:1592–1594PubMedCrossRefGoogle Scholar
  17. 17.
    Sebire NJ, Goldin RD, Regan L (2005) Term preeclampsia is associated with minimal histopathological placental features regardless of clinical severity. J Obstet Gynaecol 25:117–118PubMedCrossRefGoogle Scholar
  18. 18.
    Goswami D, Tannetta DS, Magee LA et al (2006) Excess syncytiotrophoblast microparticle shedding is a feature of early-onset pre-eclampsia, but not normotensive intrauterine growth restriction. Placenta 27:56–61PubMedCrossRefGoogle Scholar
  19. 19.
    Egbor M, Ansari T, Morris N et al (2006) Morphometric placental villous and vascular abnormalities in early- and late-onset pre-eclampsia with and without fetal growth restriction. BJOG 113:580–589PubMedCrossRefGoogle Scholar
  20. 20.
    Ness RB, Roberts JM (1996) Heterogeneous causes constituting the single syndrome of preeclampsia: a hypothesis and its implications. Am J Obstet Gynecol 175:1365–1370PubMedCrossRefGoogle Scholar
  21. 21.
    Zwahlen M, Gerber S, Bersinger NA (2007) First trimester markers for pre-eclampsia: placental vs. non-placental protein serum levels. Gynecol Obstet Invest 63:15–21PubMedCrossRefGoogle Scholar
  22. 22.
    Nicolaides KH, Bindra R, Turan OM et al (2006) A novel approach to first-trimester screening for early pre-eclampsia combining serum PP-13 and Doppler ultrasound. Ultrasound Obstet Gynecol 27:13–17PubMedCrossRefGoogle Scholar
  23. 23.
    Spencer K, Cowans NJ, Chefetz I et al (2007) First-trimester maternal serum PP-13, PAPP-A and second-trimester uterine artery Doppler pulsatility index as markers of pre-eclampsia. Ultrasound Obstet Gynecol 29:128–134PubMedCrossRefGoogle Scholar
  24. 24.
    Chafetz I, Kuhnreich I, Sammar M et al (2007) First-trimester placental protein 13 screening for preeclampsia and intrauterine growth restriction. Am J Obstet Gynecol 197:35–37PubMedCrossRefGoogle Scholar
  25. 25.
    Romero R, Kusanovic JP, Than NG et al (2008) First trimester maternal serum PP13 in the risk assessment for preeclampsia. Am J Obstet Gynecol 199(2):122.e1–122.e11PubMedCrossRefGoogle Scholar
  26. 26.
    Bohn H, Kraus W, Winckler W (1983) Purification and characterization of two new soluble placental tissue proteins (PP13 and PP17). Oncodev Biol Med 4:343–350PubMedGoogle Scholar
  27. 27.
    Than GN, Bohn H, Szabo DG (1993) Advances in pregnancy-related protein research. CRC, Boca RatonGoogle Scholar
  28. 28.
    Than NG, Sumegi B, Than GN et al (1999) Isolation and sequence analysis of a cDNA encoding human placental tissue protein 13 (PP13), a new lysophospholipase, homologue of human eosinophil Charcot-Leyden Crystal protein. Placenta 20:703–710PubMedCrossRefGoogle Scholar
  29. 29.
    Than NG, Pick E, Bellyei S et al (2004) Functional analyses of placental protein 13/galectin-13. Eur J Biochem 271:1065–1078PubMedCrossRefGoogle Scholar
  30. 30.
    Burger O, Pick E, Zwickel J et al (2004) Placental protein 13 (PP-13): effects on cultured trophoblasts, and its detection in human body fluids in normal and pathological pregnancies. Placenta 25:608–622PubMedCrossRefGoogle Scholar
  31. 31.
    Visegrady B, Than NG, Kilar F et al (2001) Homology modelling and molecular dynamics studies of human placental tissue protein 13 (galectin-13). Protein Eng 14:875–880PubMedCrossRefGoogle Scholar
  32. 32.
    Barondes SH, Castronovo V, Cooper DN et al (1994) Galectins: a family of animal beta-galactoside-binding lectins. Cell 76:597–598PubMedCrossRefGoogle Scholar
  33. 33.
    Papp Cs, Szabo G, Toth-Pal E et al (1991) Fetal growth rate and its variations 1988/89. Orv Hetil 132:1865–1870PubMedGoogle Scholar
  34. 34.
    ACOG (2002) ACOG practice bulletin: Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002. Obstet Gynecol 99:159–167CrossRefGoogle Scholar
  35. 35.
    Barton JR, Sibai BM (2004) Diagnosis and management of hemolysis, elevated liver enzymes, and low platelets syndrome. Clin Perinatol 31:807–833 viiPubMedCrossRefGoogle Scholar
  36. 36.
    Khong TY (2001) A topographical and clinical approach to examination of the placenta. Pathology 33:174–186PubMedCrossRefGoogle Scholar
  37. 37.
    Redline RW, Boyd T, Campbell V et al (2004) Maternal vascular underperfusion: nosology and reproducibility of placental reaction patterns. Pediatr Dev Pathol 7:237–249PubMedGoogle Scholar
  38. 38.
    Langston C, Kaplan C, Macpherson T et al (1997) Practice guideline for examination of the placenta: developed by the Placental Pathology Practice Guideline Development Task Force of the College of American Pathologists. Arch Pathol Lab Med 121:449–476PubMedGoogle Scholar
  39. 39.
    Hargitai B, Marton T, Cox PM (2004) Best practice no 178. Examination of the human placenta. J Clin Pathol 57:785–792PubMedCrossRefGoogle Scholar
  40. 40.
    Ogawa M, Yanoma S, Nagashima Y et al (2007) Paradoxical discrepancy between the serum level and the placental intensity of PP5/TFPI-2 in preeclampsia and/or intrauterine growth restriction: possible interaction and correlation with glypican-3 hold the key. Placenta 28:224–232PubMedCrossRefGoogle Scholar
  41. 41.
    Paradela A, Bravo SB, Henriquez M et al (2005) Proteomic analysis of apical microvillous membranes of syncytiotrophoblast cells reveals a high degree of similarity with lipid rafts. J Proteome Res 4:2435–2441PubMedCrossRefGoogle Scholar
  42. 42.
    Jones CJ, Carter AM, Aplin JD et al (2007) Glycosylation at the fetomaternal interface in hemomonochorial placentae from five widely separated species of mammal: is there evidence for convergent evolution? Cells Tissues Organs 185:269–284PubMedCrossRefGoogle Scholar
  43. 43.
    Nickel W (2005) Unconventional secretory routes: direct protein export across the plasma membrane of mammalian cells. Traffic 6:607–614PubMedCrossRefGoogle Scholar
  44. 44.
    Danielsen EM, Hansen GH (2006) Lipid raft organization and function in brush borders of epithelial cells. Mol Membr Biol 23:71–79PubMedCrossRefGoogle Scholar
  45. 45.
    Aplin JD, Straszewski-Chavez SL, Kalionis B et al (2006) Trophoblast differentiation: progenitor cells, fusion and migration—a workshop report. Placenta 27(Suppl A):S141–S143PubMedCrossRefGoogle Scholar
  46. 46.
    Knerr I, Beinder E, Rascher W (2002) Syncytin, a novel human endogenous retroviral gene in human placenta: evidence for its dysregulation in preeclampsia and HELLP syndrome. Am J Obstet Gynecol 186:210–213PubMedCrossRefGoogle Scholar
  47. 47.
    Lee X, Keith JC Jr, Stumm N et al (2001) Downregulation of placental syncytin expression and abnormal protein localization in pre-eclampsia. Placenta 22:808–812PubMedCrossRefGoogle Scholar
  48. 48.
    Langbein M, Strick R, Strissel PL et al (2008) Impaired cytotrophoblast cell-cell fusion is associated with reduced Syncytin and increased apoptosis in patients with placental dysfunction. Mol Reprod Dev 75:175–183PubMedCrossRefGoogle Scholar
  49. 49.
    Benirschke K, Kaufmann P (2000) Pathology of the human placenta, 4th edn. Springer, New YorkGoogle Scholar
  50. 50.
    Gude NM, Roberts CT, Kalionis B et al (2004) Growth and function of the normal human placenta. Thromb Res 114:397–407PubMedCrossRefGoogle Scholar
  51. 51.
    Bischof P, Irminger-Finger I (2005) The human cytotrophoblastic cell, a mononuclear chameleon. Int J Biochem Cell Biol 37:1–16PubMedCrossRefGoogle Scholar
  52. 52.
    Jones CJ, Fox H (1980) An ultrastructural and ultrahistochemical study of the human placenta in maternal pre-eclampsia. Placenta 1:61–76PubMedCrossRefGoogle Scholar
  53. 53.
    de Luca Brunori I, Battini L, Brunori E et al (2005) Placental barrier breakage in preeclampsia: ultrastructural evidence. Eur J Obstet Gynecol Reprod Biol 118:182–189PubMedCrossRefGoogle Scholar
  54. 54.
    Crocker I (2007) Pre-eclampsia and villous trophoblast turnover: perspectives and possibilities. Placenta 28(Suppl A):S4–S13PubMedCrossRefGoogle Scholar
  55. 55.
    Redman CW, Sargent IL (2007) Microparticles and immunomodulation in pregnancy and pre-eclampsia. J Reprod Immunol 76:61–67PubMedCrossRefGoogle Scholar
  56. 56.
    Mayhew TM, Wadrop E, Simpson RA (1994) Proliferative versus hypertrophic growth in tissue subcompartments of human placental villi during gestation. J Anat 184(Pt 3):535–543PubMedGoogle Scholar
  57. 57.
    Rigo J Jr, Nagy B, Fintor L et al (2000) Maternal and neonatal outcome of preeclamptic pregnancies: the potential roles of factor V Leiden mutation and 5,10 methylenetetrahydrofolate reductase. Hypertens Pregnancy 19:163–172PubMedCrossRefGoogle Scholar
  58. 58.
    Lachmeijer AM, Arngrimsson R, Bastiaans EJ et al (2001) A genome-wide scan for preeclampsia in the Netherlands. Eur J Hum Genet 9:758–764PubMedCrossRefGoogle Scholar
  59. 59.
    van Dijk M, Mulders J, Poutsma A, Könst AA et al (2005) Maternal segregation of the Dutch preeclampsia locus at 10q22 with a new member of the winged helix gene family. Nat Genet 37:514–519PubMedCrossRefGoogle Scholar
  60. 60.
    Sziller I, Babula O, Hupuczi P et al (2007) Mannose-binding lectin (MBL) codon 54 gene polymorphism protects against development of pre-eclampsia, HELLP syndrome and pre-eclampsia-associated intrauterine growth restriction. Mol Hum Reprod 13:281–285PubMedCrossRefGoogle Scholar
  61. 61.
    Oudejans CB, van DM, Oosterkamp M et al (2007) Genetics of preeclampsia: paradigm shifts. Hum Genet 120:607–612PubMedCrossRefGoogle Scholar
  62. 62.
    Cross JC (2003) The genetics of pre-eclampsia: a feto-placental or maternal problem? Clin Genet 64:96–103PubMedCrossRefGoogle Scholar

Copyright information

© US Government (NIH) 2008

Authors and Affiliations

  • Nandor Gabor Than
    • 1
    • 6
  • Omar Abdul Rahman
    • 2
  • Rita Magenheim
    • 3
  • Balint Nagy
    • 1
  • Tibor Fule
    • 4
  • Beata Hargitai
    • 4
  • Marei Sammar
    • 5
  • Petronella Hupuczi
    • 1
  • Adi L. Tarca
    • 6
  • Gabor Szabo
    • 1
  • Ilona Kovalszky
    • 4
  • Hamutal Meiri
    • 5
  • Istvan Sziller
    • 1
  • Janos Rigo Jr.
    • 1
  • Roberto Romero
    • 6
  • Zoltan Papp
    • 1
  1. 1.First Department of Obstetrics and GynecologySemmelweis UniversityBudapestHungary
  2. 2.Department of Medical Chemistry, Molecular Biology and PathobiochemistrySemmelweis UniversityBudapestHungary
  3. 3.First Department of Internal MedicineSemmelweis UniversityBudapestHungary
  4. 4.First Department of Pathology and Experimental Cancer ResearchSemmelweis UniversityBudapestHungary
  5. 5.Diagnostic Technologies LtdYokneamIsrael
  6. 6.Perinatology Research Branch, NICHD/NIH/DHHSWayne State University/Hutzel Women’s HospitalDetroitUSA

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