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.
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Achache H, Revel A. Endometrial receptivity markers, the journey to successful embryo implantation. Hum Reprod Update. 2006;12(6):731–46.
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.
Cakmak H, Taylor HS. Implantation failure: molecular mechanisms and clinical treatment. Hum Reprod Update. 2010;17(2):242–253.
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.
Quinn CE, Casper RF. Pinopodes: a questionable role in endometrial receptivity. Hum Reprod Update. 2009;15(2):229–236.
Porter MB. Ultrasound in assisted reproductive technology. Semin Reprod Med. 2008;26(3):266–276.
Kodaman PH, Taylor HS. Hormonal regulation of implantation. Obstet Gynecol Clin North Am. 2004;31(4):745–766, ix.
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.
Lessey BA. The role of the endometrium during embryo implantation. Hum Reprod. 2000;15(suppl 6):39–50.
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.
Giudice LC. Application of functional genomics to primate endometrium: insights into biological processes. Reprod Biol Endocrinol. 2006;4(suppl 1):S4.
Giudice LC. Microarray expression profiling reveals candidate genes for human uterine receptivity. Am J Pharmacogenomics. 2004;4(5):299–312.
Garrido-Gomez T, Dominguez F, Simon C. Proteomics of embryonic implantation. Handb Exp Pharmacol. 2010;198(1): 67–78.
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.
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.
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.
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.
Gardiner-Garden M, Littlejohn TG. A comparison of microarray databases. Brief Bioinform. 2001;2(2):143–158.
Olson NE, Kozlowski J, Porter S, Smith T. GeneSifter, not so blind after all. Pigment Cell Melanoma Res. 2009;22(5): 649–650.
Urbanski HF, Noriega NC, Lemos DR, Kohama SG. Gene expression profiling in the rhesus macaque: experimental design considerations. Methods. 2009;49(1):26–31.
Cardell LO, Andersson M, Cervin A, et al. Genes regulating molecular and cellular functions in noninfectious nonallergic rhinitis. Allergy. 2009;64(9):1301–1308.
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.
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.
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.
Calvano SE, Xiao W, Richards DR, et al. A network-based analysis of systemic inflammation in humans. Nature. 2005; 437(7061): 1032–1037.
Noyes RW, Hertig AT, Rock J. Dating the endometrial biopsy. Am J Obstet Gynecol. 1975;122(2):262–263.
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.
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.
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.
Aghajanova L. Leukemia inhibitory factor and human embryo implantation. Ann N Y Acad Sci. 2004;1034(1):176–183.
Rackow BW, Taylor HS. Submucosal uterine leiomyomas have a global effect on molecular determinants of endometrial receptivity. Fertil Steril. 2010;93(6):2027–2034.
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.
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.
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.
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.
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.
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.
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.
Farfalli VI, Magli MC, Ferraretti AP, Gianaroli L. Role of aneuploidy on embryo implantation. Gynecol Obstet Invest. 2007;64(3):161–165.
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.
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.
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.
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.
Girardi G, Bulla R, Salmon JE, Tedesco F. The complement system in the pathophysiology of pregnancy. Mol Immunol. 2006; 43(1–2):68–77.
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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
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DOI: https://doi.org/10.1177/1933719112442248