Skip to main content
SpringerLink
Log in

Data Mining of Spatial-Temporal Expression of Genes in the Human Endometrium During the Window of Implantation

  • Original Articles
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Previous studies of microarrays have produced mass data that are far from fully applied. To make full use of the available mass data and to avoid redundancy and unnecessary waste, we employed bioinformatics tools GeneSifter and Ingenuity Pathway Analysis (IPA) to mine and annotate 45 microarrays related to endometrium receptivity from GEO (Gene Expression Omnibus) database. In total, 1543 gene sets were found to express differentially, of which 148 highly regulated genes were listed as potential biomarkers of the receptive endometrium. The function and pathway analysis identified the differentially expressed genes primarily involved in immune response and cell cycle. Two networks related to the cardiovascular system and cancers were generated within the genes which changed more than 10-fold. Nine genes were validated by real-time polymerase chain reaction. It was a meaningful exploration of the existing data to acquire useful and reliable information, and our results undoubtedly provided valuable clues for further studies.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Achache H, Revel A. Endometrial receptivity markers, the journey to successful embryo implantation. Hum Reprod Update. 2006;12(6):731–46.

    Article  PubMed  Google Scholar 

  2. Wilcox AJ, Baird DD, Weinberg CR. Time of implantation of the conceptus and loss of pregnancy. N Engl J Med. 1999;340(23): 1796–1799.

    Article  CAS  PubMed  Google Scholar 

  3. Cakmak H, Taylor HS. Implantation failure: molecular mechanisms and clinical treatment. Hum Reprod Update. 2010;17(2):242–253.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Salamonsen LA, Nie G, Hannan NJ, Dimitriadis E. Society for reproductive biology founders’ lecture 2009. Preparing fertile soil: the importance of endometrial receptivity. Reprod Fertil Dev. 2009;21(7):923–934.

    Article  CAS  PubMed  Google Scholar 

  5. Quinn CE, Casper RF. Pinopodes: a questionable role in endometrial receptivity. Hum Reprod Update. 2009;15(2):229–236.

    Article  CAS  PubMed  Google Scholar 

  6. Porter MB. Ultrasound in assisted reproductive technology. Semin Reprod Med. 2008;26(3):266–276.

    Article  PubMed  Google Scholar 

  7. Kodaman PH, Taylor HS. Hormonal regulation of implantation. Obstet Gynecol Clin North Am. 2004;31(4):745–766, ix.

    Article  PubMed  Google Scholar 

  8. Nikas G, Drakakis P, Loutradis D, et al. Uterine pinopodes as markers of the ‘nidation window’ in cycling women receiving exogenous oestradiol and progesterone. Hum Reprod. 1995;10(5): 1208–1213.

    Article  CAS  PubMed  Google Scholar 

  9. Lessey BA. The role of the endometrium during embryo implantation. Hum Reprod. 2000;15(suppl 6):39–50.

    PubMed  Google Scholar 

  10. Boomsma CM, Kavelaars A, Eijkemans MJ, et al. Cytokine profiling in endometrial secretions: a non-invasive window on endometrial receptivity. Reprod Biomed Online. 2009;18(1):85–94.

    Article  CAS  PubMed  Google Scholar 

  11. Giudice LC. Application of functional genomics to primate endometrium: insights into biological processes. Reprod Biol Endocrinol. 2006;4(suppl 1):S4.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Giudice LC. Microarray expression profiling reveals candidate genes for human uterine receptivity. Am J Pharmacogenomics. 2004;4(5):299–312.

    Article  CAS  PubMed  Google Scholar 

  13. Garrido-Gomez T, Dominguez F, Simon C. Proteomics of embryonic implantation. Handb Exp Pharmacol. 2010;198(1): 67–78.

    Article  CAS  Google Scholar 

  14. Kao LC, Tulac S, Lobo S, et al. Global gene profiling in human endometrium during the window of implantation. Endocrinology. 2002;143(6):2119–2138.

    Article  CAS  PubMed  Google Scholar 

  15. Borthwick JM, Charnock-Jones DS, Tom BD, et al. Determination of the transcript profile of human endometrium. Mol Hum Reprod. 2003;9(1):19–33.

    Article  CAS  PubMed  Google Scholar 

  16. Mirkin S, Arslan M, Churikov D, et al. In search of candidate genes critically expressed in the human endometrium during the window of implantation. Hum Reprod. 2005;20(8):2104–2117.

    Article  CAS  PubMed  Google Scholar 

  17. Talbi S, Hamilton AE, Vo KC, et al. Molecular phenotyping of human endometrium distinguishes menstrual cycle phases and underlying biological processes in normo-ovulatory women. Endocrinology. 2006;147(3):1097–1121.

    Article  CAS  PubMed  Google Scholar 

  18. Gardiner-Garden M, Littlejohn TG. A comparison of microarray databases. Brief Bioinform. 2001;2(2):143–158.

    Article  CAS  PubMed  Google Scholar 

  19. Olson NE, Kozlowski J, Porter S, Smith T. GeneSifter, not so blind after all. Pigment Cell Melanoma Res. 2009;22(5): 649–650.

    Article  PubMed  Google Scholar 

  20. Urbanski HF, Noriega NC, Lemos DR, Kohama SG. Gene expression profiling in the rhesus macaque: experimental design considerations. Methods. 2009;49(1):26–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Cardell LO, Andersson M, Cervin A, et al. Genes regulating molecular and cellular functions in noninfectious nonallergic rhinitis. Allergy. 2009;64(9):1301–1308.

    Article  CAS  PubMed  Google Scholar 

  22. Burney RO, Talbi S, Hamilton AE, et al. Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis. Endocrinology. 2007;148(8):3814–3826.

    Article  CAS  PubMed  Google Scholar 

  23. Hever A, Roth RB, Hevezi P, et al. Human endometriosis is associated with plasma cells and overexpression of B lymphocyte stimulator. Proc Natl Acad Sci U S A. 2007;104(30): 12451–12456.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Van Vaerenbergh I, Van Lommel L, Ghislain V, et al. In GnRH antagonist/rec-FSH stimulated cycles, advanced endometrial maturation on the day of oocyte retrieval correlates with altered gene expression. Hum Reprod. 2009;24(5):1085–1091.

    Article  PubMed  CAS  Google Scholar 

  25. Calvano SE, Xiao W, Richards DR, et al. A network-based analysis of systemic inflammation in humans. Nature. 2005; 437(7061): 1032–1037.

    Article  CAS  PubMed  Google Scholar 

  26. Noyes RW, Hertig AT, Rock J. Dating the endometrial biopsy. Am J Obstet Gynecol. 1975;122(2):262–263.

    Article  CAS  PubMed  Google Scholar 

  27. Diedrich K, Fauser BC, Devroey P, Griesinger G. The role of the endometrium and embryo in human implantation. Hum Reprod Update. 2007;13(4):365–377.

    Article  CAS  PubMed  Google Scholar 

  28. Carson DD, Lagow E, Thathiah A, et al. Changes in gene expression during the early to mid-luteal (receptive phase) transition in human endometrium detected by high-density microarray screening. Mol Hum Reprod. 2002;8(9):871–879.

    Article  CAS  PubMed  Google Scholar 

  29. Riesewijk A, Martin J, van Os R, et al. Gene expression profiling of human endometrial receptivity on days LH+2 versus LH+7 by microarray technology. Mol Hum Reprod. 2003;9(5): 253–264.

    Article  CAS  PubMed  Google Scholar 

  30. Aghajanova L. Leukemia inhibitory factor and human embryo implantation. Ann N Y Acad Sci. 2004;1034(1):176–183.

    Article  CAS  PubMed  Google Scholar 

  31. Rackow BW, Taylor HS. Submucosal uterine leiomyomas have a global effect on molecular determinants of endometrial receptivity. Fertil Steril. 2010;93(6):2027–2034.

    Article  CAS  PubMed  Google Scholar 

  32. Kutsukake M, Tamura K, Yoshie M, Tachikawa E. Knockdown of IGF-binding protein 7 inhibits transformation of the endometrial gland in an in vitro model. Mol Reprod Dev. 2010;77(3):265–272.

    CAS  PubMed  Google Scholar 

  33. Zhang SY, Lin XN, Song T, et al. [Gene expression profiles of peri-implantation endometrium in natural and superovulation cycles]. Zhonghua YiXue Za Zhi. 2008;88(33):2343–2346.

    CAS  PubMed  Google Scholar 

  34. Tong XM, Lin XN, Song T, Liu L, Zhang SY. Calcium-binding protein S100P is highly expressed during the implantation window in human endometrium. Fertil Steril. 2009;94(4): 1510–1518.

    Article  PubMed  CAS  Google Scholar 

  35. Tseng LH, Chen I, Chen MY, et al. Genome-based expression profiling as a single standardized microarray platform for the diagnosis of endometrial disorder: an array of 126-gene model. Fertil Steril. 2010;94(1): 114–119.

    Article  CAS  PubMed  Google Scholar 

  36. Dassen H, Punyadeera C, Kamps R, et al. Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007;64(7–8):1009–1032.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Yamauchi T, Hara K, Maeda S, et al. A genome-wide association study in the Japanese population identifies susceptibility loci for type 2 diabetes at UBE2E2 and C2CD4A-C2CD4B. Nat Genet. 2010;42(10):864–868.

    Article  CAS  PubMed  Google Scholar 

  38. Warton K, Foster NC, Gold WA, Stanley KK. A novel gene family induced by acute inflammation in endothelial cells. Gene. 2004;342(1):85–95.

    Article  CAS  PubMed  Google Scholar 

  39. Farfalli VI, Magli MC, Ferraretti AP, Gianaroli L. Role of aneuploidy on embryo implantation. Gynecol Obstet Invest. 2007;64(3):161–165.

    Article  CAS  PubMed  Google Scholar 

  40. Fauzdar A, Sharma RK, Kumar A, Haider A. A preliminary study on chromosome aneuploidy & mosaicism in early pre-implantation human embryo by fluorescence in situ hybridization. Indian J Med Res. 2008;128(3):287–293.

    PubMed  Google Scholar 

  41. Yaron Y, Ochshorn Y, Amit A, et al. Patients with Turner’s syndrome may have an inherent endometrial abnormality affecting receptivity in oocyte donation. Fertil Steril. 1996;65(6): 1249–1252.

    Article  CAS  PubMed  Google Scholar 

  42. Nogawa Fonzar-Marana RR, Ferriani RA, Soares SG, et al. Expression of complement system regulatory molecules in the endometrium of normal ovulatory and hyperstimulated women correlate with menstrual cycle phase. Fertil Steril. 2006;86(3): 758–761.

    Article  PubMed  Google Scholar 

  43. Hasty LA, Lambris JD, Lessey BA, Pruksananonda K, Lyttle CR. Hormonal regulation of complement components and receptors throughout the menstrual cycle. Am J Obstet Gynecol. 1994; 170(1 pt 1):168–175.

    Article  CAS  PubMed  Google Scholar 

  44. Girardi G, Bulla R, Salmon JE, Tedesco F. The complement system in the pathophysiology of pregnancy. Mol Immunol. 2006; 43(1–2):68–77.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Obstetrics and Gynecology Hospital, Fudan University, 413 Zhaozhou Road, 200011, Shanghai, China

    Dan Zhang MD & Wei Zhang PhD

  2. Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China

    Cuixiang Sun MD

  3. Health Center for Women and Children, Chang ning district, Shanghai, China

    Chengbin Ma MD

  4. Pu Nan Hospital, Shanghai, China

    Haiyan Dai MD

Authors
  1. Dan Zhang MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cuixiang Sun MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chengbin Ma MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Haiyan Dai MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wei Zhang PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wei Zhang PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, D., Sun, C., Ma, C. et al. Data Mining of Spatial-Temporal Expression of Genes in the Human Endometrium During the Window of Implantation. Reprod. Sci. 19, 1085–1098 (2012). https://doi.org/10.1177/1933719112442248

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719112442248

Keywords

Search

Navigation