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Cytokine-related genes and oxidation-related genes detected in preeclamptic placentas

Archives of Gynecology and Obstetrics volume 282, pages 363–369 (2010)Cite this article

Abstract

Purpose

To investigate cytokine- and oxidation-related genes for preeclampsia using DNA microarray analysis.

Methods

Placentas were collected from 13 normal pregnancies and 13 patients with preeclampsia. Gene expression was studied using DNA microarray. Among significantly expressed genes, we focused on genes associated with cytokines and oxidation, and the results were confirmed using quantitative real time-polymerase chain reaction (QRT-PCR).

Results

415 genes out of 30,940 genes were altered by ≥2-fold in the microarray analysis. 121 up-regulated genes and 294 down-regulated genes were found to be in preeclamptic placenta. Six cytokine-related genes and 5 oxidation-related genes were found from among the 121 up-regulated genes. The cytokine-related genes studied included oncostatin M (OSM), fms-related tyrosine kinase (FLT1) and vascular endothelial growth factor A (VEGFA), and the oxidation-related genes studied included spermine oxidase (SMOX), l cytochrome P450, family 26, subfamily A, polypeptide 1 (CYP26A1), acetate dehydrogenase A (LDHA). These six genes were also significantly higher in placentas from patients with preeclampsia than in those from women with normal pregnancies. The placental tissue of patients with preeclampsia showed significantly higher mRNA expression of these six genes than the normal group, using QRT-PCR.

Conclusion

DNA microarray analysis is one of the great methods for simultaneously detecting the functionally associated genes of preeclampsia. The cytokine-related genes such as OSM, FLT1 and VEGFA, and the oxidation-related genes such as LDHA, CYP26A1 and SMOX might prove to be the starting point in the elucidation of the pathogenesis of preeclampsia.

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References

  1. Roberts JM, Cooper DW (2001) Pathogenesis and genetics of pre-eclampsia. Lancet 357:53–56

    CAS  Article  PubMed  Google Scholar 

  2. Han JY, Kim YS, Cho GJ, Roh GS, Kim HJ, Choi WJ, Paik WY, Rho GJ, Kang SS, Choi WS (2006) Altered gene expression of caspase-10, death receptor-3 and igfbp-3 in preeclamptic placentas. Mol Cells 22:168–174

    CAS  PubMed  Google Scholar 

  3. Lachmeijer AM, Dekker GA, Pals G, Aarnoudse JG, ten Kate LP, Arngrimsson R (2002) Searching for preeclampsia genes: the current position. Eur J Obstet Gynecol Reprod Biol 105:94–113

    CAS  PubMed  Google Scholar 

  4. Nishizawa H, Pryor-Koishi K, Kato T, Kowa H, Kurahashi H, Udagawa Y (2007) Microarray analysis of differentially expressed fetal genes in placental tissue derived from early and late onset severe pre-eclampsia. Placenta 28:487–497

    CAS  Article  PubMed  Google Scholar 

  5. Pang ZJ, Xing FQ (2003) Comparative study on the expression of cytokine-receptor genes in normal and preeclamptic human placentas using DNA microarrays. J Perinat Med 31:153–162

    CAS  Article  PubMed  Google Scholar 

  6. Reimer T, Koczan D, Gerber B, Richter D, Thiesen HJ, Friese K (2002) Microarray analysis of differentially expressed genes in placental tissue of pre-eclampsia: up-regulation of obesity-related genes. Mol Hum Reprod 8:674–680

    CAS  Article  PubMed  Google Scholar 

  7. Soleymanlou N, Jurisica I, Nevo O, Ietta F, Zhang X, Zamudio S, Post M, Caniggia I (2005) Molecular evidence of placental hypoxia in preeclampsia. J Clin Endocrinol Metab 90:4299–4308

    CAS  Article  PubMed  Google Scholar 

  8. Tsoi SC, Cale JM, Bird IM, Kay HH (2003) cDNA microarray analysis of gene expression profiles in human placenta: up-regulation of the transcript encoding muscle subunit of glycogen phosphorylase in preeclampsia. J Soc Gynecol Invest 10:496–502

    CAS  Article  Google Scholar 

  9. Zhou R, Zhu Q, Wang Y, Ren Y, Zhang L, Zhou Y (2006) Genomewide oligonucleotide microarray analysis on placentae of pre-eclamptic pregnancies. Gynecol Obstet Invest 62:108–114

    CAS  Article  PubMed  Google Scholar 

  10. Taylor RN, Heilbron DC, Roberts JM (1990) Growth factor activity in the blood of women in whom preeclampsia develops is elevated from early pregnancy. Am J Obstet Gynecol 163:1839–1844

    CAS  PubMed  Google Scholar 

  11. Greer IA, Lyall F, Perera T, Boswell F, Macara LM (1994) Increased concentrations of cytokines interleukin-6 and interleukin-1 receptor antagonist in plasma of women with preeclampsia: a mechanism for endothelial dysfunction? Obstet Gynecol 84:937–940

    CAS  PubMed  Google Scholar 

  12. Hubel CA (1998) Dyslipidemia, iron, and oxidative stress in preeclampsia: assessment of maternal and feto-placental interactions. Semin Reprod Endocrinol 16:75–92

    CAS  Article  PubMed  Google Scholar 

  13. Pang ZJ, Xing FQ (2004) DNA microarrays detect the expression of apoptosis-related genes in preeclamptic placentas. J Perinat Med 32:25–30

    CAS  Article  PubMed  Google Scholar 

  14. Heikkila A, Tuomisto T, Hakkinen SK, Keski-Nisula L, Heinonen S, Yla-Herttuala S (2005) Tumor suppressor and growth regulatory genes are overexpressed in severe early-onset preeclampsia––an array study on case-specific human preeclamptic placental tissue. Acta Obstet Gynecol Scand 84:679–689

    PubMed  Google Scholar 

  15. Enquobahrie DA, Meller M, Rice K, Psaty BM, Siscovick DS, Williams MA (2008) Differential placental gene expression in preeclampsia. Am J Obstet Gynecol 199:566 e1–11

    Article  PubMed  Google Scholar 

  16. Pang ZJ, Xing FQ (2004) Comparative profiling of metabolism-related gene expression in pre-eclamptic and normal pregnancies. Arch Gynecol Obstet 269:91–95

    CAS  Article  PubMed  Google Scholar 

  17. Schulpis KH, Vlachos GD, Karikas GA, Papakonstantinou ED, Vlachos DG, Papassotiriou I, Antsaklis A, Tsakiris S (2008) The effect of the mode of delivery on maternal–neonatal interleukin-6, biogenic amine and their precursor amino acid concentrations. Clin Chem Lab Med 46:1624–1630

    CAS  Article  PubMed  Google Scholar 

  18. Schulpis KH, Papakonstantinou ED, Vlachos GD, Vlachos DG, Antsaklis A, Papassotiriou I, Tsakiris S (2008) The effect of the mode of delivery on the maternal–neonatal carnitine blood levels and antioxidant status. Clin Chem Lab Med 46:680–686

    CAS  Article  PubMed  Google Scholar 

  19. Anteby EY, Ayesh S, Shochina M, Hamani Y, Schneider T, Al-Shareef W, Hochberg A, Ariel I (2005) Growth factor receptor-protein bound 2 (grb2) upregulation in the placenta in preeclampsia implies a possible role for ras signalling. Eur J Obstet Gynecol Reprod Biol 118:174–181

    CAS  Article  PubMed  Google Scholar 

  20. Gack S, Marme A, Marme F, Wrobel G, Vonderstrass B, Bastert G, Lichter P, Angel P, Schorpp-Kistner M (2005) Preeclampsia: increased expression of soluble ADAM 12. J Mol Med 83:887–896

    CAS  Article  PubMed  Google Scholar 

  21. Kendall RL, Wang G, Thomas KA (1996) Identification of a natural soluble form of the vascular endothelial growth factor receptor, FLT-1, and its heterodimerization with kdr. Biochem Biophys Res Commun 226:324–328

    CAS  Article  PubMed  Google Scholar 

  22. Rajakumar A, Brandon HM, Daftary A, Ness R, Conrad KP (2004) Evidence for the functional activity of hypoxia-inducible transcription factors overexpressed in preeclamptic placentae. Placenta 25:763–769

    CAS  Article  PubMed  Google Scholar 

  23. Gu Y, Lewis DF, Wang Y (2008) Placental productions and expressions of soluble endoglin, soluble fms-like tyrosine kinase receptor-1, and placental growth factor in normal and preeclamptic pregnancies. J Clin Endocrinol Metab 93:260–266

    CAS  Article  PubMed  Google Scholar 

  24. Jarvenpaa J, Vuoristo JT, Savolainen ER, Ukkola O, Vaskivuo T, Ryynanen M (2007) Altered expression of angiogenesis-related placental genes in pre-eclampsia associated with intrauterine growth restriction. Gynecol Endocrinol 23:351–355

    CAS  Article  PubMed  Google Scholar 

  25. Hou XH, Li DH, Li Y, Zhao HX, Zhang CL, Huang L, Yao YQ (2006) Expression of fms-like tyrosine kinase receptor 1 in placenta of pre-eclampsia. Zhonghua Fu Chan Ke Za Zhi 41:736–739

    PubMed  Google Scholar 

  26. Maynard SE, Min JY, Merchan J, Lim KH, Li J, Mondal S, Libermann TA, Morgan JP, Sellke FW, Stillman IE, Epstein FH, Sukhatme VP, Karumanchi SA (2003) Excess placental soluble fms-like tyrosine kinase 1 (sFLT1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest 111:649–658

    CAS  PubMed  Google Scholar 

  27. Geva E, Ginzinger DG, Zaloudek CJ, Moore DH, Byrne A, Jaffe RB (2002) Human placental vascular development: vasculogenic and angiogenic (branching and nonbranching) transformation is regulated by vascular endothelial growth factor-a, angiopoietin-1, and angiopoietin-2. J Clin Endocrinol Metab 87:4213–4224

    CAS  Article  PubMed  Google Scholar 

  28. Akercan F, Cirpan T, Terek MC, Ozcakir HT, Giray G, Sagol S, Karadadas N (2008) The immunohistochemical evaluation of vegf in placenta biopsies of pregnancies complicated by preeclampsia. Arch Gynecol Obstet 277:109–114

    CAS  Article  PubMed  Google Scholar 

  29. Cirpan T, Akercan F, Terek MC, Kazandi M, Ozcakir HT, Giray G, Sagol S (2007) Evaluation of VEGF in placental bed biopsies from preeclamptic women by immunohistochemistry. Clin Exp Obstet Gynecol 34:228–231

    CAS  PubMed  Google Scholar 

  30. Trollmann R, Amann K, Schoof E, Beinder E, Wenzel D, Rascher W, Dotsch J (2003) Hypoxia activates the human placental vascular endothelial growth factor system in vitro and in vivo: up-regulation of vascular endothelial growth factor in clinically relevant hypoxic ischemia in birth asphyxia. Am J Obstet Gynecol 188:517–523

    CAS  Article  PubMed  Google Scholar 

  31. Ogata I, Shimoya K, Moriyama A, Shiki Y, Matsumura Y, Yamanaka K, Nobunaga T, Tokugawa Y, Kimura T, Koyama M, Azuma C, Murata Y (2000) Oncostatin m is produced during pregnancy by decidual cells and stimulates the release of hCG. Mol Hum Reprod 6:750–757

    CAS  Article  PubMed  Google Scholar 

  32. Vasse M, Pourtau J, Trochon V, Muraine M, Vannier JP, Lu H, Soria J, Soria C (1999) Oncostatin m induces angiogenesis in vitro and in vivo. Arterioscler Thromb Vasc Biol 19:1835–1842

    CAS  PubMed  Google Scholar 

  33. Toninello A, Pietrangeli P, De Marchi U, Salvi M, Mondovi B (2006) Amine oxidases in apoptosis and cancer. Biochim Biophys Acta 1765:1–13

    CAS  PubMed  Google Scholar 

  34. Seiler N (2000) Oxidation of polyamines and brain injury. Neurochem Res 25:471–490

    CAS  Article  PubMed  Google Scholar 

  35. Averill-Bates DA, Agostinelli E, Przybytkowski E, Mondovi B (1994) Aldehyde dehydrogenase and cytotoxicity of purified bovine serum amine oxidase and spermine in Chinese hamster ovary cells. Biochem Cell Biol 72:36–42

    CAS  Article  PubMed  Google Scholar 

  36. Thornberry NA, Rosen A, Nicholson DW (1997) Control of apoptosis by proteases. Adv Pharmacol 41:155–177

    CAS  Article  PubMed  Google Scholar 

  37. Chamy VM, Lepe J, Catalan A, Retamal D, Escobar JA, Madrid EM (2006) Oxidative stress is closely related to clinical severity of pre-eclampsia. Biol Res 39:229–236

    CAS  Article  PubMed  Google Scholar 

  38. Redman CW, Sargent IL (2001) The pathogenesis of pre-eclampsia. Gynecol Obstet Fertil 29:518–522

    CAS  Article  PubMed  Google Scholar 

  39. Jendryczko A, Drozdz M (1989) Plasma retinol, beta-carotene and vitamin e levels in relation to the future risk of pre-eclampsia. Zentralbl Gynakol 111:1121–1123

    CAS  PubMed  Google Scholar 

  40. Tsoi SC, Zheng J, Xu F, Kay HH (2001) Differential expression of lactate dehydrogenase isozymes (LDH) in human placenta with high expression of LDHA(4) isozyme in the endothelial cells of pre-eclampsia villi. Placenta 22:317–322

    CAS  Article  PubMed  Google Scholar 

  41. Kay HH, Zhu S, Tsoi S (2007) Hypoxia and lactate production in trophoblast cells. Placenta 28:854–860

    CAS  Article  PubMed  Google Scholar 

  42. Founds SA, Dorman JS, Conley YP (2008) Microarray technology applied to the complex disorder of preeclampsia. J Obstet Gynecol Neonatal Nurs 37:146–157

    Article  PubMed  Google Scholar 

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Affiliations

  1. Department of Obstetrics and Gynecology, Catholic University of Korea, Soechoe-dong, Banpo-gu, Seoul, Republic of Korea

    Gui Se Ra Lee, Yoon Seong Joe, Sa Jin Kim & Jong Chul Shin

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  1. Gui Se Ra Lee
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  2. Yoon Seong Joe
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  3. Sa Jin Kim
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  4. Jong Chul Shin
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Correspondence to Jong Chul Shin.

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Lee, G.S.R., Joe, Y.S., Kim, S.J. et al. Cytokine-related genes and oxidation-related genes detected in preeclamptic placentas. Arch Gynecol Obstet 282, 363–369 (2010). https://doi.org/10.1007/s00404-009-1222-x

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  • DOI: https://doi.org/10.1007/s00404-009-1222-x

Keywords

  • Preeclampsia
  • Placenta
  • Cytokine-related genes
  • Oxidation-related genes