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Altered gene profile of placenta from women with intrahepatic cholestasis of pregnancy

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Abstract

Objectives

To investigate the alterations in gene profile of placenta from pregnant women with intrahepatic cholestasis of pregnancy (ICP) and to enhance the insight of etiology and pathogenesis of ICP.

Methods

Ten pregnant women diagnosed ICP were recruited and 10 healthy pregnant women served as control. Four samples were taken from each placenta and RNA was isolated. Gene expression was analyzed with microarray and real time PCR was used to validate the differentially expressed genes.

Results

392 genes were found differentially expressed. Among these differentially expressed genes, 280 were up-regulated and 112 were down-regulated. These differentially expressed genes involved 20 categories including genes involved in transportation, cell growth, apoptosis and immune response that were putatively participated the pathogenesis of ICP.

Conclusions

293 differentially expressed genes of 20 categories were found in ICP placenta, suggesting the diversity of gene expression alteration and the complexity of etiology and pathogenesis of ICP.

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References

  1. Lammert F, Marschall HU, Glantz A, Matern S (2000) Intrahepatic cholestasis of pregnancy: molecular pathogenesis, diagnosis and management. J Hepatol 33(6):1012–1021

    Article  CAS  PubMed  Google Scholar 

  2. Beuers U, Pusl T (2006) Intrahepatic cholestasis of pregnancy—a heterogeneous group of pregnancy-related disorders? Hepatology 43(4):647–649

    Article  CAS  PubMed  Google Scholar 

  3. Riely CA, Bacq Y (2004) Intrahepatic cholestasis of pregnancy. Clin liver dis 8(1):167–176

    Article  PubMed  Google Scholar 

  4. Fisk NM, Storey GN (1988) Fetal outcome in obstetric cholestasis. Br J Obstet Gynaecol 95(11):1137–1143

    CAS  PubMed  Google Scholar 

  5. Bacq Y, Sapey T, Bréchot MC, Pierre F, Fignon A, Dubois F (1997) Intrahepatic cholestasis of pregnancy: a French prospective study. Hepatology 26(2):358–364

    Article  CAS  PubMed  Google Scholar 

  6. Rioseco AJ, Ivankovic MB, Manzur A et al (1994) Intrahepatic cholestasis of pregnancy: a retrospective case-control study of perinatal outcome. Am J Obstet Gynecol 170(3):890–895

    CAS  PubMed  Google Scholar 

  7. Laatikainen T, Ikonen E (1975) Fetal prognosis in obstetric hepatosis. Ann Chir Gynaecol Fenn 64(3):155–164

    CAS  PubMed  Google Scholar 

  8. Shaw D, Frohlich J, Wittmann BA, Willms M (1982) A prospective study of 18 patients with cholestasis of pregnancy. Am J Obstet Gynecol 142(6 Pt 1):621–625

    CAS  PubMed  Google Scholar 

  9. Alsulyman OM, Ouzounian JG, Ames-Castro M, Goodwin TM (1996) Intrahepatic cholestasis of pregnancy: perinatal outcome associated with expectant management. Am J Obstet Gynecol 175(4 Pt 1):957–960

    Article  CAS  PubMed  Google Scholar 

  10. Williamson C, Hems LM, Goulis DG et al (2004) Clinical outcome in a series of cases of obstetric cholestasis identified via a patient support group. BJOG 111(7):676–681

    Article  PubMed  Google Scholar 

  11. Zhao YJ, Yue YF, Liu XQ, Li SH, Liu ZY, Wang Y (2004) Study on relationship between serum cholylglycine and placental apoptosis in patients with intrahepatic cholestasis of pregnancy (in Chinese). Zhonghua Fu Chan Ke Za Zhi 39(7):446–448

    PubMed  Google Scholar 

  12. Wang DM, La XL, Ding L (2003) Study on apoptosis and expression of Fas, FasL in placenta of intrahepatic cholestasis of pregnancy (in Chinese). Chin J Perinat Med 6(4):199–201

    Google Scholar 

  13. Zhang SJ (2007) Immunohistochemical study on the expression of TNF-α in placenta in intrahepatic cholestasis of pregnancy (in Chinese). Acta Acad Med Xuzhou 27(7):451–452

    CAS  Google Scholar 

  14. Dong MY, He J, Wang ZP (2003) Placental expression of epidermal growth factor receptor in intrahepatic cholestasis of pregnancy. Chin J Obstet Gynecol 38(2):106–107

    Google Scholar 

  15. Watson A, Mazumder A, Stewart M, Balasubramanian S (1998) Technology for microarray analysis of gene expression. Curr Opin Biotechnol 9:609–614

    Article  CAS  PubMed  Google Scholar 

  16. Smith L, Greenfield A (2003) DNA microarrays and development. Hum Mol Genet 12(1):R1–R8

    Article  CAS  PubMed  Google Scholar 

  17. Schena M, Shalon D, Davis RW, Brown PO (1995) Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 270(20):467–470

    Article  CAS  PubMed  Google Scholar 

  18. Dong M, Shi Y (1996) Evaluation of cholic glycine in serum and hemorrheological parameters in women with intrahepatic cholestasis of pregnancy (in Chinese). Curr Adv Obstet Gynecol 5:251–253

    Google Scholar 

  19. Dong M, Wang Z, He J, Shi Y, Yang P, Pan Y (1999) Increased anticardiolipin antibody in intrahepatic cholestasis of pregnancy (in Chinese). Chin J Obstet Gynecol 34:491

    Google Scholar 

  20. Dong M, Xie X, Wang Z, He J, Zhou J (2002) Impaired mixed lymphocyte reaction in intrahepatic cholestasis of pregnancy (in Chinese). Gynecol Obstet Invest 54:191–195

    Article  PubMed  Google Scholar 

  21. Cristofalo VJ (2000) A DNA chip off aging block. Nat Med 6(5):507

    Article  CAS  PubMed  Google Scholar 

  22. Wang ZP, Dong MY, Chu HN, He J (2004) Increased serum levels of neopterin and soluble interleukin-2 receptor in intrahepatic cholestasis of pregnancy. Acta Obstet Gynecol Scand 83(11):1067–1070

    PubMed  Google Scholar 

  23. Peng B, Liu SY (2002) Study of relationship between T helper cell type1 and type2 cytokines and intrahepatic cholestasis of pregnancy (in Chinese). Zhonghua Fu Chan Ke Za Zhi 37(9):516–518

    PubMed  Google Scholar 

  24. Ling B, Yao FQ, Zhou Y, Chen ZZ, Shen GD, Zhu YY (2007) Cell-mediated immunity imbalance in patients with intrahepatic cholestasis of pregnancy. Cell Mol Immunol 4(1):71–75

    CAS  PubMed  Google Scholar 

  25. Koehler LH, Benz EJ (1962) Serum adenosine deaminase: methodology and clinical applications. Clin Chem 8:133–140

    CAS  PubMed  Google Scholar 

  26. Ungerer JP, Oosthuizen HM, Bissbort SH, Vermaak WJ (1992) Serum adenosine deaminase: isoenzymes and diagnostic application. Clin Chem 38(7):1322–1326

    CAS  PubMed  Google Scholar 

  27. Trajkovic V, Sweet MJ, Xu D (2004) T1/ST2—an IL-1 receptor-like modulator of immune responses. Cytokine Growth Factor Rev 15(2–3):87–95

    Article  CAS  PubMed  Google Scholar 

  28. Xu D, Chan WL, Leung BP et al (1998) Selective expression of a stable cell surface molecule on type 2 but not type 1 helper T cells. J Exp Med 187(5):787–794

    Article  CAS  PubMed  Google Scholar 

  29. Löhning M, Stroehmann A, Coyle AJ et al (1998) T1/ST2 is preferentially expressed on murine Th2 cells, independent of interleukin 4, interleukin 5, and interleukin 10, and important for Th2 effector function. Proc Natl Acad Sci USA 95(12):6930–6935

    Article  PubMed  Google Scholar 

  30. Coyle AJ, Lloyd C, Tian J et al (1999) Crucial role of the interleukin 1 receptor family member T1/ST2 in T helper cell type 2-mediated lung mucosal immune responses. J Exp Med 190(7):895–902

    Article  CAS  PubMed  Google Scholar 

  31. Dann AT, Kenyon AP, Wierzbicki AS, Seed PT, Shennan AH, Tribe RM (2006) Plasma lipid profiles of women with intrahepatic cholestasis of pregnancy. Obstet Gynecol 107(1):106–114

    CAS  PubMed  Google Scholar 

  32. Spreyer P, Schaal H, Kuhn G et al (1990) Regeneration-associated high level expression of apolipoprotein D mRNA in endoneurial fibroblasts of peripheral nerve. EMBO J 9(8):2479–2484

    CAS  PubMed  Google Scholar 

  33. Xia SY, Chen ZQ, Li L (2003) Change of vascular endothelial growth factor (VEGF) and its significance in placenta for patients with intrahepatic cholestasis in pregnancy (in Chinese). J Chin Phys 5(8):1068–1070

    Google Scholar 

  34. Liu JP, Baker J, Perkins AS, Robertson EJ, Efstratiadis A (1993) Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r). Cell 75(1):59–72

    CAS  PubMed  Google Scholar 

  35. DeChiara TM, Efstratiadis A, Robertson EJ (1990) A growth-deficiency phenotype in heterozygous mice carrying an insulin-like growth factor II gene disrupted by targeting. Nature 345(6270):78–80

    Article  CAS  PubMed  Google Scholar 

  36. Lin CG, Leu SJ, Chen N et al (2003) CCN3 (NOV) is a novel angiogenic regulator of the CCN protein family. J Biol Chem 278(26):24200–24208

    Article  CAS  PubMed  Google Scholar 

  37. Ellis PD, Chen Q, Barker PJ, Metcalfe JC, Kemp PR (2000) Nov gene encodes adhesion factor for vascular smooth muscle cells and is dynamically regulated in response to vascular injury. Arterioscler Thromb Vasc Biol 20(8):1912–1919

    CAS  PubMed  Google Scholar 

  38. Gellhaus A, Schmidt M, Dunk C, Lye SJ, Kimmig R, Winterhager E (2006) Decreased expression of the angiogenic regulators CYR61 (CCN1) and NOV (CCN3) in human placenta is associated with pre-eclampsia. Mol Hum Reprod 12(6):389–399

    Article  CAS  PubMed  Google Scholar 

  39. Chen M, Sun LZ, Ding HJ, Wu WP (2007) The relationship between intrahepatic cholestasis and placenta cells apoptosis in pregnancy (in Chinese). Mod Med J 35(6):428–431

    Google Scholar 

  40. Perez MJ, Macias RI, Marin JJ (2006) Maternal cholestasis induces placental oxidative stress and apoptosis. Protective effect of ursodeoxycholic acid. Placenta 27(1):34–41

    Article  CAS  PubMed  Google Scholar 

  41. Huang JR, Liu J, Chang SF (2006) Mechanism of farnesoid X receptor and bile salt excretory pump on bile acid transport in placenta of intrahepatic cholestasis of pregnany (in Chinese). Chongqing Med J 174:9–1950

    Google Scholar 

  42. Floreani A, Carderi I, Paternoster D et al (2008) Hepatobiliary phospholipid transporter ABCB4, MDR3 gene variants in a large cohort of Italian women with intrahepatic cholestasis of pregnancy. Dig Liver Dis 40(5):366–370

    Article  CAS  PubMed  Google Scholar 

  43. Arrese M, Macias RI, Briz O, Perez MJ, Marin JJ (2008) Molecular pathogenesis of intrahepatic cholestasis of pregnancy. Expert Rev Mol Med 28:10:e9

    Google Scholar 

  44. Serrano MA, Macias RIR, Briz O et al (2007) Expression in human trophoblast and choriocarcinoma cell lines, BeWo, Jeg-3 and JAr of genes involved in the hepatobiliary-like excretory function of the placenta. Placenta 28:107–117

    Article  CAS  PubMed  Google Scholar 

  45. Patel P, Weerasekera N, Hitchins M, Boyd CAR, Johnston DG, Williamson C (2003) Semi quantitative expression analysis of MDR3, FIC1, BSEP, OATP-A, OATP-C, OATP-D, OATP-E and NTCP gene transcripts in 1st and 3rd trimester human placenta. Placenta 24:39–44

    Article  CAS  PubMed  Google Scholar 

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Acknowledgment

This study was financially supported by ZJNSF (No Y205297).

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Correspondence to Zhengping Wang.

Additional information

J. Wei and H. Wang were contributed equally.

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Wei, J., Wang, H., Yang, X. et al. Altered gene profile of placenta from women with intrahepatic cholestasis of pregnancy. Arch Gynecol Obstet 281, 801–810 (2010). https://doi.org/10.1007/s00404-009-1156-3

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  • DOI: https://doi.org/10.1007/s00404-009-1156-3

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