Skip to main content
Log in

Role of oxidative stress in the pathogenesis of preeclampsia

  • Materno-fetal Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Hypertensive disorders of pregnancy are associated with an increased risk of maternal and fetal morbidity and mortality. The cause and the pathogenesis of the pregnancy-induced syndrome, preeclampsia, is still poorly understood. Published evidence of altered biomarkers for the endothelial dysfunction suggests that the initiating event in preeclampsia is the reduced placental perfusion, which leads to widespread dysfunction of the maternal vascular endothelium. This review focuses on the role of free radicals in generating the oxidative stress taking antioxidants into consideration which tend to overcome it as well as the role of placenta in preeclamptic pregnancy.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Roberts JM, Taylor RN, Musci TJ, Rodgers GM, Hubel CA, McLaughlin MK (1989) Preeclampsia: an endothelial cell disorder. Am J Obstet Gynecol 161(5):1200–1204

    CAS  PubMed  Google Scholar 

  2. Cnossen JS, Vollebregt KC, de Vrieze N, ter Riet G, Mol BW, Franx A et al (2008) Accuracy of mean arterial pressure and blood pressure measurements in predicting preeclampsia: systematic review and meta-analysis. BMJ 336(7653):1117–1120

    Article  PubMed  Google Scholar 

  3. North RA, Taylor RS, Schellenberg JC (1999) Evaluation of a definition of preeclampsia. Br J Obstet Gynaecol 106(8):767–773

    CAS  PubMed  Google Scholar 

  4. Peter Stein T, Scholl TO, Schluter MD, Leskiw MJ, Chen X, Spur BW et al (2008) Oxidative stress early in pregnancy and pregnancy outcome. Free Radic Res 42(10):841–848

    Article  CAS  PubMed  Google Scholar 

  5. Terry MB, Flom J, Tehranifar P, Susser E (2009) The role of birth cohorts in studies of adult health: the New York women’s birth cohort. Paediatr Perinat Epidemiol 23(5):431–445

    Article  PubMed  Google Scholar 

  6. Joern H, Rath W (2000) Correlation of Doppler velocimetry findings in twin pregnancies including course of pregnancy and fetal outcome. Fetal Diagn Ther 15(3):160–164

    Article  CAS  PubMed  Google Scholar 

  7. Redman CW, Sargent IL (2009) Placental stress and preeclampsia: a revised view. Placenta 30(Suppl A):S38–S42

    Article  PubMed  Google Scholar 

  8. Goldman-Wohl D, Yagel S (2009) Preeclampsia–a placenta developmental biology perspective. J Reprod Immunol 82(2):96–99

    Article  CAS  PubMed  Google Scholar 

  9. Valko M, Morris H, Cronin MT (2005) Metals, toxicity and oxidative stress. Curr Med Chem 12(10):1161–1208

    Article  CAS  PubMed  Google Scholar 

  10. Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M (2006) Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 160(1):1–40

    Article  CAS  PubMed  Google Scholar 

  11. Bobba A, Atlante A, Petragallo VA, Marra E (2008) Different sources of reactive oxygen species contribute to low potassium-induced apoptosis in cerebellar granule cells. Int J Mol Med 21(6):737–745

    CAS  PubMed  Google Scholar 

  12. Halliwell B, Gutteridge JM (1990) Role of free radicals and catalytic metal ions in human disease: an overview. Meth Enzymol 186:1–85

    Article  CAS  PubMed  Google Scholar 

  13. Nakamura Y, Takahashi K, Satoh K, Shimetani A, Sakagami H, Nishikawa H (2006) Role of free radicals and metal ions in direct current-induced cytotoxicity. J Endod 32(5):442–446

    Article  PubMed  Google Scholar 

  14. Sies H (1997) Oxidative stress: oxidants and antioxidants. Exp Physiol 82(2):291–295

    CAS  PubMed  Google Scholar 

  15. Rahman K (2007) Studies on free radicals, antioxidants, and co-factors. Clin Interv Aging 2(2):219–236

    CAS  PubMed  Google Scholar 

  16. Gutteridge JM (1995) Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clin Chem 41(12 Pt 2):1819–1828

    CAS  PubMed  Google Scholar 

  17. Padayatty SJ, Katz A, Wang Y, Eck P, Kwon O, Lee JH et al (2003) Vitamin C as an antioxidant: evaluation of its role in disease prevention. J Am Coll Nutr 22(1):18–35

    CAS  PubMed  Google Scholar 

  18. Serdar Z, Gur E, Colakoethullary M, Develioethlu O, Sarandol E (2003) Lipid and protein oxidation and antioxidant function in women with mild and severe preeclampsia. Arch Gynecol Obstet 268(1):19–25

    CAS  PubMed  Google Scholar 

  19. Trejo-Solis C, Chagoya De Sanchez V, Aranda-Fraustro A, Sanchez-Sevilla L, Gomez-Ruiz C, Hernandez-Munoz R (2003) Inhibitory effect of vitamin e administration on the progression of liver regeneration induced by partial hepatectomy in rats. Lab Invest 83(11):1669–1679

    Article  CAS  PubMed  Google Scholar 

  20. Ishihara M (1978) Studies on lipoperoxide of normal pregnant women and of patients with toxemia of pregnancy. Clin Chim Acta 84(1–2):1–9

    CAS  PubMed  Google Scholar 

  21. Kaur G, Mishra S, Sehgal A, Prasad R (2008) Alterations in lipid peroxidation and antioxidant status in pregnancy with preeclampsia. Mol Cell Biochem 313(1–2):37–44

    Article  CAS  PubMed  Google Scholar 

  22. Fridovich I (1979) Hypoxia and oxygen toxicity. Adv Neurol 26:255–259

    CAS  PubMed  Google Scholar 

  23. Dotsch J, Hogen N, Nyul Z, Hanze J, Knerr I, Kirschbaum M et al (2001) Increase of endothelial nitric oxide synthase and endothelin-1 mRNA expression in human placenta during gestation. Eur J Obstet Gynecol Reprod Biol 97(2):163–167

    Article  CAS  PubMed  Google Scholar 

  24. Jones DP (2008) Radical-free biology of oxidative stress. Am J Physiol Cell Physiol 295(4):C849–C868

    Article  CAS  PubMed  Google Scholar 

  25. Wisdom SJ, Wilson R, McKillop JH, Walker JJ (1991) Antioxidant systems in normal pregnancy and in pregnancy-induced hypertension. Am J Obstet Gynecol 165(6 Pt 1):1701–1704

    CAS  PubMed  Google Scholar 

  26. Ilouno LE, Shu EN, Igbokwe GE (1996) An improved technique for the assay of red blood cell superoxide dismutase (SOD) activity. Clin Chim Acta 247(1–2):1–6

    Article  CAS  PubMed  Google Scholar 

  27. Qanungo S, Mukherjea M (2000) Ontogenic profile of some antioxidants and lipid peroxidation in human placental and fetal tissues. Mol Cell Biochem 215(1–2):11–19

    Article  CAS  PubMed  Google Scholar 

  28. Watson AL, Skepper JN, Jauniaux E, Burton GJ (1998) Changes in concentration, localization and activity of catalase within the human placenta during early gestation. Placenta 19(1):27–34

    Article  CAS  PubMed  Google Scholar 

  29. Tamura T, Olin KL, Goldenberg RL, Johnston KE, Dubard MB, Keen CL (2001) Plasma extracellular superoxide dismutase activity in healthy pregnant women is not influenced by zinc supplementation. Biol Trace Elem Res 80(2):107–113

    Article  CAS  PubMed  Google Scholar 

  30. Romero R, Chaiworapongsa T, Espinoza J (2003) Micronutrients and intrauterine infection, preterm birth and the fetal inflammatory response syndrome. J Nutr 133(5 Suppl 2):1668S–1673S

    CAS  PubMed  Google Scholar 

  31. Chappell LC, Seed PT, Briley AL, Kelly FJ, Lee R, Hunt BJ et al (1999) Effect of antioxidants on the occurrence of preeclampsia in women at increased risk: a randomised trial. Lancet 354(9181):810–816

    Article  CAS  PubMed  Google Scholar 

  32. Dordevic NZ, Babic GM, Markovic SD, Ognjanovic BI, Stajn AS, Zikic RV et al (2008) Oxidative stress and changes in antioxidative defense system in erythrocytes of preeclampsia in women. Reprod Toxicol 25(2):213–218

    Article  PubMed  Google Scholar 

  33. Rumbold A, Duley L, Crowther CA, Haslam RR (2008) Antioxidants for preventing pre-eclampsia. Cochrane Database Syst Rev (1):CD004227

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

    Article  PubMed  Google Scholar 

  35. Myatt L (2002) Role of placenta in preeclampsia. Endocrine 19(1):103–111

    Article  CAS  PubMed  Google Scholar 

  36. van Asselt K, Gudmundsson S, Lindqvist P, Marsal K (1998) Uterine and umbilical artery velocimetry in pre-eclampsia. Acta Obstet Gynecol Scand 77(6):614–619

    Article  PubMed  Google Scholar 

  37. Patil SB, Kodliwadmath MV, Kodliwadmath M (2009) Lipid peroxidation and antioxidant activity in complicated pregnancies. Clin Exp Obstet Gynecol 36(2):110–112

    CAS  PubMed  Google Scholar 

  38. Orhan H, Onderoglu L, Yucel A, Sahin G (2003) Circulating biomarkers of oxidative stress in complicated pregnancies. Arch Gynecol Obstet 267(4):189–195

    CAS  PubMed  Google Scholar 

  39. Fiore G, Capasso A (2008) Effects of vitamin E and C on placental oxidative stress: an in vitro evidence for the potential therapeutic or prophylactic treatment of preeclampsia. Med Chem 4(6):526–530

    Article  CAS  PubMed  Google Scholar 

  40. Rosta K, Molvarec A, Enzsoly A, Nagy B, Ronai Z, Fekete A et al (2009) Association of extracellular superoxide dismutase (SOD3) Ala40Thr gene polymorphism with pre-eclampsia complicated by severe fetal growth restriction. Eur J Obstet Gynecol Reprod Biol 142(2):134–138

    CAS  PubMed  Google Scholar 

  41. Yoder SR, Thornburg LL, Bisognano JD (2009) Hypertension in pregnancy and women of childbearing age. Am J Med 122(10):890–895

    Article  PubMed  Google Scholar 

  42. Zhang Y, Zhao S, Gu Y, Lewis DF, Alexander JS, Wang Y (2005) Effects of peroxynitrite and superoxide radicals on endothelial monolayer permeability: potential role of peroxynitrite in preeclampsia. J Soc Gynecol Investig 12(8):586–592

    Article  CAS  PubMed  Google Scholar 

  43. Sankaralingam S, Arenas IA, Lalu MM, Davidge ST (2006) Preeclampsia: current understanding of the molecular basis of vascular dysfunction. Expert Rev Mol Med 8(3):1–20

    Article  PubMed  Google Scholar 

  44. Aris A, Benali S, Ouellet A, Moutquin JM, Leblanc S (2009) Potential biomarkers of preeclampsia: inverse correlation between hydrogen peroxide and nitric oxide early in maternal circulation and at term in placenta of women with preeclampsia. Placenta 30(4):342–347

    Article  CAS  PubMed  Google Scholar 

  45. O’Riordan MN, Higgins JR (2003) Haemostasis in normal and abnormal pregnancy. Best Pract Res Clin Obstet Gynaecol 17(3):385–396

    Article  PubMed  Google Scholar 

  46. Paternoster DM, Fantinato S, Manganelli F, Milani M, Nicolini U, Girolami A (2004) Efficacy of AT in preeclampsia: a case-control prospective trial. Thromb Haemost 91(2):283–289

    CAS  PubMed  Google Scholar 

  47. Rousseau A, Favier R, Van Dreden P (2009) Elevated circulating soluble thrombomodulin activity, tissue factor activity and circulating procoagulant phospholipids: new and useful markers for preeclampsia? Eur J Obstet Gynecol Reprod Biol 146(1):46–49

    Article  CAS  PubMed  Google Scholar 

  48. Shaarawy M, Didy HE (1996) Thrombomodulin, plasminogen activator inhibitor type 1 (PAI-1) and fibronectin as biomarkers of endothelial damage in preeclampsia and eclampsia. Int J Gynaecol Obstet 55(2):135–139

    Article  CAS  PubMed  Google Scholar 

  49. Molvarec A, Rigo J Jr, Boze T, Derzsy Z, Cervenak L, Mako V et al (2009) Increased plasma von Willebrand factor antigen levels but normal von Willebrand factor cleaving protease (ADAMTS13) activity in preeclampsia. Thromb Haemost 101(2):305–311

    CAS  PubMed  Google Scholar 

  50. Liu Q, Yan X, Li Y, Zhang Y, Zhao X, Shen Y (2004) Preeclampsia is associated with the failure of melanoma cell adhesion molecule (MCAM/CD146) expression by intermediate trophoblast. Lab Invest 84(2):221–228

    Article  CAS  PubMed  Google Scholar 

  51. Horstman LL, Jy W, Jimenez JJ, Ahn YS (2004) Endothelial microparticles as markers of endothelial dysfunction. Front Biosci 9:1118–1135

    Article  CAS  PubMed  Google Scholar 

  52. Portelinha A, Belo L, Tejera E, Rebelo I (2008) Adhesion molecules (VCAM-1 and ICAM-1) and C-reactive protein in women with history of preeclampsia. Acta Obstet Gynecol Scand 87(9):969–971

    Article  CAS  PubMed  Google Scholar 

  53. Krauss T, Azab H, Dietrich M, Augustin HG (1998) Fetal plasma levels of circulating endothelial cell adhesion molecules in normal and preeclamptic pregnancies. Eur J Obstet Gynecol Reprod Biol 78(1):41–45

    Article  CAS  PubMed  Google Scholar 

  54. Hanisch CG, Pfeiffer KA, Schlebusch H, Schmolling J (2004) Adhesion molecules, activin and inhibin—candidates for the biochemical prediction of hypertensive diseases in pregnancy? Arch Gynecol Obstet 270(2):110–115

    Article  CAS  PubMed  Google Scholar 

  55. Molvarec A, Rigo J Jr, Lazar L, Balogh K, Mako V, Cervenak L et al (2009) Increased serum heat-shock protein 70 levels reflect systemic inflammation, oxidative stress and hepatocellular injury in preeclampsia. Cell Stress Chaperones 14(2):151–159

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest statement

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Imran A. Siddiqui.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Siddiqui, I.A., Jaleel, A., Tamimi, W. et al. Role of oxidative stress in the pathogenesis of preeclampsia. Arch Gynecol Obstet 282, 469–474 (2010). https://doi.org/10.1007/s00404-010-1538-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-010-1538-6

Keywords

Navigation