Skip to main content


Log in

Proliferation of trophoblasts and Ki67 expression in preeclampsia

  • Maternal-Fetal Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript



Preeclampsia is a pregnancy-specific disease with the increased risk of maternal morbidity and mortality. It is characterised by placental vascular dysfunction. Despite the numerous studies on preeclampsia, studies evaluating proliferation of villous trophoblasts in preeclamptic placentas are limited. Ki67 is a proliferation marker that expresses in the nuclei of proliferating cells. In this study, we examined the proliferation of villous trophoblasts in placentas of preeclamptic patients by using Ki67 and compared it with placentas of normal pregnant patients.

Material and methods

The current study is a prospective one, including 15 placentas from preeclamptic patients and 14 placentas from normal pregnancies as controls. For detection of proliferation in villous trophoblasts, Ki67 was used.


The Ki67 index was 11.48±1.67% in normal patients and 15.53±2.28% in preeclamptic patients. There was a difference in Ki67 index between the two groups (p < 0.001).


Our results support the opinion that trophoblasts undergo regeneration hyperplasia as a result of injuries arising on the villous surface in preeclampsia. Proliferation of trophoblasts may contribute the development of preeclampsia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others


  1. Sibai BM (2005) Magnesium sulfate prophylaxis in preeclampsia: evidence from randomized trials. Clin Obstet Gynecol 48(2):478–488

    Article  PubMed  Google Scholar 

  2. Mohaupt M (2007) Molecular aspects of preeclampsia. Mol Asp Med 28(2):169–191

    Article  CAS  Google Scholar 

  3. Higgins JR, de Swiet M (2001) Blood pressure measurement and classification in pregnancy. Lancet 357(9250):131–135

    Article  CAS  PubMed  Google Scholar 

  4. Redman CWG, Sargent IL (2001) The pathogenesis of pre-eclampsia. Gynecol Obstet Fertil 29(7–8):518–522

    Article  CAS  PubMed  Google Scholar 

  5. Granger JP, Joey P, Alexander BT, Llinas MT, Benett WA, Khalil RA (2002) Pathophysiology of preeclampsia: linking placental ischemia/hypoxia with microvascular dysfunction. Microcirculation 9(3):147–160

    Article  CAS  PubMed  Google Scholar 

  6. Brosenes IA, Robertson WB, Dixon HG (1972) The role of spiral arteries in the pathogenesis of preeclampsia. In: Wynn RM (ed) Obstetrics and gynecology annual. Appleton-Century-Crofts, New York, pp 177–191

    Google Scholar 

  7. Madazlı R, Budak E, Calay Z, Aksu MF (2000) Correlation between placental bed biopsy findings, vascular cell adhesion molecule (VCAM-1) and fibronectin levels in preeclampsia. BJOG 107(4):514–518

    Article  PubMed  Google Scholar 

  8. Madazlı R, Benian A, Aydın S, Uzun S, Tolun N (2002) The plasma and placental levels of malondialdehyde, glutathione and superoxide dismutase in preeclampsia. J Obstet Gynecol 22(5):477–480

    Article  Google Scholar 

  9. Madazlı R, Somunkiran A, Calay Z, Ilvan S, Aksu MF (2003) Histomorphology of the placenta and the placental bed of growth restricted foetuses and correlation with the Doppler velocimetries of the uterine and umbilical arteries. Placenta 24(5):510–516

    Article  PubMed  Google Scholar 

  10. Hung TH, Burton GJ (2006) Hypoxia-reoxygenation; a possible mechanism for placental oxidative stress in preeclampsia. Tawain J Obstet Gynecol 45(3):189–200

    Article  Google Scholar 

  11. Raymond W, Redline MD, Patterson BS (1995) Pre-eclampsia is associated with an excess of proliferative immature intermediate trophoblast. Hum Pathol 26(6):594–600

    Article  Google Scholar 

  12. Scholzen T, Gerdes J (2000) The Ki-67 protein: from the known and the unknown. J Cell Physiol 182(3):311–322

    Article  CAS  PubMed  Google Scholar 

  13. ACOG Committe on Obstetric Practice, ACOG practice bulletin (2002) Diagnosis and management of pre-eclampsia and eclampsia. In J Gynaecol Obstet 77(1):67–75

    Google Scholar 

  14. Raymond D, Peterson E (2011) A critical review of early-onset and late-onset preeclampsia. Obstet Gynecol Surv 66(8):497–506

    Article  PubMed  Google Scholar 

  15. Benirschke K, Kaufmann P (1995) Basic structure of the villous tree. In: Kaufmann P (ed) Pathology of the placenta, 3rd edn. Springer Verlag, New York, pp 71–79

    Chapter  Google Scholar 

  16. Simpson RA, Mayhew TM, Barnes PR (1992) From 13 weeks to term, the trophoblast of human placenta grows by continuous recruitment of new proliferative unit: a study of nuclear number using dissector. Placenta 13(5):501–502

    Article  CAS  PubMed  Google Scholar 

  17. Mochizuki M, Maruo T, Samoto T, Ishihara N (1998) Biology of human trophoblast. Int J Gynaecol Obstet 60(Suppl 1):S21–S28

    Article  PubMed  Google Scholar 

  18. Genbacev O, McMaster MT, Fischer SJ (2000) A repertoire of cell cycle regulators whose expression is coordinated with human cytotrophoblast differentiation. Am J Pathol 157:1337–1351

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Suresh UR, Hale RJ, Fox H, Buckley CH (1993) Use of proliferation cell nuclear antigen immunoreactivity for distinguishing hydropic abortions from partial hydatidiform moles. J Clin Pathol 46(1):48–50

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Arnholdt H, Meisel F, Fandrey K, Löhrs U (1991) Proliferation of villous trophoblast of the human placenta in normal and abnormal pregnancies. Virchow Archiv B Cell Pathology 60(6):365–372

    Article  CAS  Google Scholar 

  21. Soma H, Yoshida K, Mukaida T, Tabuchi Y (1982) Morphologic changes in the hypertensive placenta. Contr Gynecol Obstet 9:58–75

    CAS  Google Scholar 

  22. Teadstale F (1985) Histomorphometry of the human placenta in maternal preeclampsia. Am J Obstet Gynecol 152(1):25–31

    Article  Google Scholar 

  23. Hustin J, Foidart JM, Lambotte R (1984) Cellular proliferation in villi of normal and pathological pregnancies. Gynecol Obstet Invest 17(1):1–9

    Article  CAS  PubMed  Google Scholar 

  24. Unek G, Ozmen A, Mendilcioglu I, Simsek M, Korgun ET (2014) Immunohistochemical distribution of cell cycle proteins p27, p57, cyclin D3, PCNA and Ki67 in normal and diabetic human placentas. J Mol Hist 45:21–34

    Article  CAS  Google Scholar 

  25. Unek G, Ozmen A, Ozekinci M, Sakinci M, Korgun ET (2014) Immunolocalization of cell cycle proteins (p57, p27, cyclin D3, PCNA and Ki67) in intrauterine growth retardation (IUGR) and normal human term placentas. Acta Histochem 116:493–502

    Article  CAS  PubMed  Google Scholar 

  26. Jeschke U, Schiessl B, Mylonas I, Kunze S, Kuhn C, Schulze S et al (2006) Expression of the proliferation marker Ki-67 and p53 tumor protein in trophoblastic tissue of preeclamptic, HELLP, and intrauterine growth-restricted pregnancies. Int J Gynecolo Pathol 25(4):354–360

    Article  Google Scholar 

  27. Thomas SZ, Prusac IK, Roje D, Tadin I (2011) Trophoblast apoptosis in placentae from pregnancies complicated by preeclampsia. Gynecol Obstet Invest 71(4):250–255

    Article  Google Scholar 

  28. Prusac IK (2011) Zekic Tomas S, Roje D. Apoptosis, proliferation and Fas ligand expression in placental trophoblast from pregnancies complicated by HELLP syndrome or preeclampsia. Acta Obstet Gynecol Scand 90(10):1157–1163

    Article  CAS  PubMed  Google Scholar 

  29. Unek G, Oxmen A, Mendilcioglu I, Simsek M, Korgun ET (2014) The expression of cell cycle related proteins PCNA, Ki67, p27 and p57 in normal and preeclamptic human placentas. Tissue Cell 46:198–205

    Article  CAS  PubMed  Google Scholar 

  30. Elpek GÜ, Karaveli Ş, Keleş N (2000) Preeklampsili olguların term plasentalarında villöz trofoblast proliferasyonunun incelenmesi (Evaluation of proliferation of villous trophoblasts in term placentae of preeclamptic patients). Turkish J Pathol 16(1–2):10–12

    Google Scholar 

  31. Lyall F, Myatt L (2002) The role of placenta in pre-eclampsia-a workshop report. Placenta 23:142–145

    Article  Google Scholar 

  32. Redline RW, Patterson P (1995) Pre-eclampsia is associated with an excess of proliferative immature intermediate trophoblast. Hum Pathol 26:594–600

    Article  CAS  PubMed  Google Scholar 

  33. Kaltenbach FJ, Fettig O, Krieger ML (1974) Autoradiographische untersuchungen über das proliferationsverhalten der menschlichen placenta unter normalen und pathologischen bedingungen [Radioautographic observations on DNA-synthesis in the human placenta under normal and pathologic conditions (author’s transl). Arch Gynakol 216(4):369–386

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest


Author information

Authors and Affiliations


Corresponding author

Correspondence to Umit Nayki.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kaya, B., Nayki, U., Nayki, C. et al. Proliferation of trophoblasts and Ki67 expression in preeclampsia. Arch Gynecol Obstet 291, 1041–1046 (2015).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: