Molecular Human Reproduction, Vol. 9, No. 5, 253-264,
May 2003
© 2003 European Society of Human Reproduction and Embryology
Article |
Gene expression profiling of human endometrial receptivity on days LH+2 versus LH+7 by microarray technology
Submitted on July 18, 2002; resubmitted on January 18, 2003;. accepted on January 22, 2003
1 NV Organon, Departments of Target Discovery & Pharmacology, Oss, The Netherlands, 2 Foundation of the Instituto Valenciano de Infertilidad and 3 Department of Pediatrics, Obstetrics and Gynecology, Valencia University School of Medicine, Valencia, Spain
4 To whom correspondence should be addressed at: Plaza de la Policia Local 3, 46015 Valencia, Spain. e-mail: csimon{at}interbook.net
In humans, embryonic implantation and reproduction depends on the interaction of the embryo with the receptive endometrium. To gain a global molecular understanding of human endometrial receptivity, we compared gene expression profiles of pre-receptive (day LH+2) versus receptive (LH+7) endometria obtained from the same fertile woman (n = 5) in the same menstrual cycle in five independent experiments. Biopsies were analysed using the Affymetrix HG-U95A array, a DNA chip containing 
12 000 genes. Using the pre-defined criteria of a fold change 
3 in at least four out of five women, we identified 211 regulated genes. Of these, 153 were up-regulated at LH+7 versus LH+2, whereas 58 were down-regulated. Amongst these 211 regulated genes, we identified genes that were known to play a role in the development of a receptive endometrium, and genes for which a role in endometrial receptivity, or even endometrial expression, has not been previously described. Validation of array data was accomplished by mRNA quantification by real time quantitative fluorescent PCR (Q-PCR) of three up-regulated [glutathione peroxidase 3 (GPx-3), claudin 4 (claudin-4) and solute carrier family 1 member 1 (SLC1A1)] genes in independent LH+2 versus LH+7 endometrial samples from fertile women (n = 3) and the three up-regulated genes throughout the menstrual cycle (n = 15). Human claudin-4 peaks specifically during the implantation window, whereas GPx-3 and SLC1A1 showed highest expression in the late secretory phase. In-situ hybridization (ISH) experiments showed that GPx-3 and SLC1A1 expression was restricted to glandular and luminal epithelial cells during the mid- and late luteal phase. The present work adds new and important data in this field, and highlights the complexity of studying endometrial receptivity even using global gene-expression analysis.
Key words: endometrium/gene expression profiles/implantation/receptivity
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  F. Dominguez, T. Garrido-Gomez, J.A. Lopez, E. Camafeita, A. Quinonero, A. Pellicer, and C. Simon Proteomic analysis of the human receptive versus non-receptive endometrium using differential in-gel electrophoresis and MALDI-MS unveils stathmin 1 and annexin A2 as differentially regulated Hum. Reprod., June 25, 2009; (2009) dep230v1. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Allegra, A. Marino, F. Coffaro, A. Lama, G. Rizza, P. Scaglione, F. Sammartano, A. Santoro, and A. Volpes Is there a uniform basal endometrial gene expression profile during the implantation window in women who became pregnant in a subsequent ICSI cycle? Hum. Reprod., June 20, 2009; (2009) dep222v1. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Haouzi, S. Assou, K. Mahmoud, S. Tondeur, T. Reme, B. Hedon, J. De Vos, and S. Hamamah Gene expression profile of human endometrial receptivity: comparison between natural and stimulated cycles for the same patients Hum. Reprod., June 1, 2009; 24(6): 1436 - 1445. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Parmar, S. Nimbkar-Joshi, R.R. Katkam, S. Gadkar-Sable, U. Chaudhari, D.D. Manjramkar, L. Savardekar, S. Jacob, C.P. Puri, and G. Sachdeva Differential expression of calreticulin, a reticuloplasmin in primate endometrium Hum. Reprod., May 21, 2009; (2009) dep187v1. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Yamagata, H. Asada, I. Tamura, L. Lee, R. Maekawa, K. Taniguchi, T. Taketani, A. Matsuoka, H. Tamura, and N. Sugino DNA methyltransferase expression in the human endometrium: down-regulation by progesterone and estrogen Hum. Reprod., May 1, 2009; 24(5): 1126 - 1132. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.E. Quinn and R.F. Casper Pinopodes: a questionable role in endometrial receptivity Hum. Reprod. Update, March 1, 2009; 15(2): 229 - 236. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. O. D. Critchley and P. T. K. Saunders Hormone Receptor Dynamics in a Receptive Human Endometrium Reproductive Sciences, February 1, 2009; 16(2): 191 - 199. [Abstract] [PDF]
|
|
|
|
|
|
D. Haouzi, K. Mahmoud, M. Fourar, K. Bendhaou, H. Dechaud, J. De Vos, T. Reme, D. Dewailly, and S. Hamamah Identification of new biomarkers of human endometrial receptivity in the natural cycle Hum. Reprod., January 1, 2009; 24(1): 198 - 205. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Toloubeydokhti, Qun Pan, Xiaoping Luo, O. Bukulmez, and N. Chegini The Expression and Ovarian Steroid Regulation of Endometrial Micro-RNAs Reproductive Sciences, December 1, 2008; 15(10): 993 - 1001. [Abstract] [PDF]
|
|
|
|
 |
|
 J. A. Horcajadas, P. Minguez, J. Dopazo, F. J. Esteban, F. Dominguez, L. C. Giudice, A. Pellicer, and C. Simon Controlled Ovarian Stimulation Induces a Functional Genomic Delay of the Endometrium with Potential Clinical Implications J. Clin. Endocrinol. Metab., November 1, 2008; 93(11): 4500 - 4510. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Horcajadas, E. Goyri, M. A. Higon, J. A. Martinez-Conejero, P. Gambadauro, G. Garcia, M. Meseguer, C. Simon, and A. Pellicer Endometrial Receptivity and Implantation Are Not Affected by the Presence of Uterine Intramural Leiomyomas: A Clinical and Functional Genomics Analysis J. Clin. Endocrinol. Metab., September 1, 2008; 93(9): 3490 - 3498. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. A. Bersinger, D. M. Wunder, M. H. Birkhauser, and M. D. Mueller Gene expression in cultured endometrium from women with different outcomes following IVF Mol. Hum. Reprod., August 1, 2008; 14(8): 475 - 484. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Franchi, J. Zaret, X. Zhang, S. Bocca, and S. Oehninger Expression of immunomodulatory genes, their protein products and specific ligands/receptors during the window of implantation in the human endometrium Mol. Hum. Reprod., July 1, 2008; 14(7): 413 - 421. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-F. Xia, J. Sun, Q.-H. Sun, Y. Yang, and J.-P. Peng Implantation-associated gene-1 (Iag-1): a novel gene involved in the early process of embryonic implantation in rat Hum. Reprod., July 1, 2008; 23(7): 1581 - 1593. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Guffanti, N. Kittur, Z. N. Brodt, A. J. Polotsky, S. M. Kuokkanen, D. S. Heller, S. L. Young, N. Santoro, and U. T. Meier Nuclear pore complex proteins mark the implantation window in human endometrium J. Cell Sci., June 15, 2008; 121(12): 2037 - 2045. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Evans, R. D. Catalano, K. Morgan, H. O. D. Critchley, R. P. Millar, and H. N. Jabbour Prokineticin 1 Signaling and Gene Regulation in Early Human Pregnancy Endocrinology, June 1, 2008; 149(6): 2877 - 2887. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. S. Macklon, M. H. van der Gaast, A. Hamilton, B. C. J. M. Fauser, and L. C. Giudice The Impact of Ovarian Stimulation With Recombinant FSH in Combination With GnRH Antagonist on the Endometrial Transcriptome in the Window of Implantation Reproductive Sciences, April 1, 2008; 15(4): 357 - 365. [Abstract] [PDF]
|
|
|
|
|
|
A. Tapia, L. M. Gangi, F. Zegers-Hochschild, J. Balmaceda, R. Pommer, L. Trejo, I. M. Pacheco, A. M. Salvatierra, S. Henriquez, M. Quezada, et al. Differences in the endometrial transcript profile during the receptive period between women who were refractory to implantation and those who achieved pregnancy Hum. Reprod., February 1, 2008; 23(2): 340 - 351. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Pan, X. Luo, T. Toloubeydokhti, and N. Chegini The expression profile of micro-RNA in endometrium and endometriosis and the influence of ovarian steroids on their expression Mol. Hum. Reprod., November 1, 2007; 13(11): 797 - 806. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Feroze-Zaidi, L. Fusi, M. Takano, J. Higham, M. S. Salker, T. Goto, S. Edassery, K. Klingel, K. M. Boini, M. Palmada, et al. Role and Regulation of the Serum- and Glucocorticoid-Regulated Kinase 1 in Fertile and Infertile Human Endometrium Endocrinology, October 1, 2007; 148(10): 5020 - 5029. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R.D. Catalano, H.O. Critchley, O. Heikinheimo, D.T. Baird, D. Hapangama, J.R.A. Sherwin, D.S. Charnock-Jones, S.K. Smith, and A.M. Sharkey Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium Mol. Hum. Reprod., September 1, 2007; 13(9): 641 - 654. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.G. Groothuis, H.H.N.M. Dassen, A. Romano, and C. Punyadeera Estrogen and the endometrium: lessons learned from gene expression profiling in rodents and human Hum. Reprod. Update, July 1, 2007; 13(4): 405 - 417. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Diedrich, B.C.J.M. Fauser, P. Devroey, G. Griesinger, and on behalf of the Evian Annual Reproduction (EVAR) The role of the endometrium and embryo in human implantation Hum. Reprod. Update, July 1, 2007; 13(4): 365 - 377. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. C Jaffe, S. D Ferguson-Gottschall, W. Gao, C. Beam, and A. T Fazleabas Histone deacetylase inhibition and progesterone act synergistically to stimulate baboon glycodelin gene expression J. Mol. Endocrinol., March 1, 2007; 38(3): 401 - 407. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.A. Horcajadas, A. Pellicer, and C. Simon Wide genomic analysis of human endometrial receptivity: new times, new opportunities Hum. Reprod. Update, January 1, 2007; 13(1): 77 - 86. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.P. Hess, A.E. Hamilton, S. Talbi, C. Dosiou, M. Nyegaard, N. Nayak, O. Genbecev-Krtolica, P. Mavrogianis, K. Ferrer, J. Kruessel, et al. Decidual Stromal Cell Response to Paracrine Signals from the Trophoblast: Amplification of Immune and Angiogenic Modulators Biol Reprod, January 1, 2007; 76(1): 102 - 117. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Henriquez, A. Tapia, M. Quezada, M. Vargas, H. Cardenas, M. Rios, A.M. Salvatierra, H. Croxatto, P. Orihuela, F. Zegers-Hochschild, et al. Deficient expression of monoamine oxidase A in the endometrium is associated with implantation failure in women participating as recipients in oocyte donation Mol. Hum. Reprod., December 1, 2006; 12(12): 749 - 754. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.P. Ponnampalam and P.A.W. Rogers Cyclic changes and hormonal regulation of annexin IV mRNA and protein in human endometrium Mol. Hum. Reprod., November 1, 2006; 12(11): 661 - 669. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E.A. Campbell, L. O'Hara, R.D. Catalano, A.M. Sharkey, T.C. Freeman, and M. H. Johnson Temporal expression profiling of the uterine luminal epithelium of the pseudo-pregnant mouse suggests receptivity to the fertilized egg is associated with complex transcriptional changes Hum. Reprod., October 1, 2006; 21(10): 2495 - 2513. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Strowitzki, A. Germeyer, R. Popovici, and M. von Wolff The human endometrium as a fertility-determining factor Hum. Reprod. Update, September 1, 2006; 12(5): 617 - 630. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bauersachs, S. E Ulbrich, K. Gross, S. E M Schmidt, H. H D Meyer, H. Wenigerkind, M. Vermehren, F. Sinowatz, H. Blum, and E. Wolf Embryo-induced transcriptome changes in bovine endometrium reveal species-specific and common molecular markers of uterine receptivity. Reproduction, August 1, 2006; 132(2): 319 - 331. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Horcajadas, A. M. Sharkey, R. D. Catalano, J. R. A. Sherwin, F. Dominguez, L. A. Burgos, A. Castro, M. R. Peraza, A. Pellicer, and C. Simon Effect of an Intrauterine Device on the Gene Expression Profile of the Endometrium J. Clin. Endocrinol. Metab., August 1, 2006; 91(8): 3199 - 3207. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Sherwin, R. Catalano, and A. Sharkey Large-scale gene expression studies of the endometrium: what have we learnt? Reproduction, July 1, 2006; 132(1): 1 - 10. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Takemura, Y. Osuga, T. Yamauchi, M. Kobayashi, M. Harada, T. Hirata, C. Morimoto, Y. Hirota, O. Yoshino, K. Koga, et al. Expression of Adiponectin Receptors and Its Possible Implication in the Human Endometrium Endocrinology, July 1, 2006; 147(7): 3203 - 3210. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. S. Macklon, R. L. Stouffer, L. C. Giudice, and B. C. J. M. Fauser The Science behind 25 Years of Ovarian Stimulation for in Vitro Fertilization Endocr. Rev., April 1, 2006; 27(2): 170 - 207. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Tulac, M. T. Overgaard, A. E. Hamilton, N. L. Jumbe, E. Suchanek, and L. C. Giudice Dickkopf-1, an Inhibitor of Wnt Signaling, Is Regulated by Progesterone in Human Endometrial Stromal Cells J. Clin. Endocrinol. Metab., April 1, 2006; 91(4): 1453 - 1461. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. A. Simmen and R. C. M. Simmen Orchestrating the Menstrual Cycle: Discerning the Music from the Noise. Endocrinology, March 1, 2006; 147(3): 1094 - 1096. [Full Text] [PDF]
|
|
|
|
|
|
S. Talbi, A. E. Hamilton, K. C. Vo, S. Tulac, M. T. Overgaard, C. Dosiou, N. Le Shay, C. N. Nezhat, R. Kempson, B. A. Lessey, et al. Molecular Phenotyping of Human Endometrium Distinguishes Menstrual Cycle Phases and Underlying Biological Processes in Normo-Ovulatory Women Endocrinology, March 1, 2006; 147(3): 1097 - 1121. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. N. Jabbour, R. W. Kelly, H. M. Fraser, and H. O. D. Critchley Endocrine Regulation of Menstruation Endocr. Rev., February 1, 2006; 27(1): 17 - 46. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Simon, J. Oberye, J. Bellver, C. Vidal, E. Bosch, J.A. Horcajadas, C. Murphy, S. Adams, A. Riesewijk, B. Mannaerts, et al. Similar endometrial development in oocyte donors treated with either high- or standard-dose GnRH antagonist compared to treatment with a GnRH agonist or in natural cycles Hum. Reprod., December 1, 2005; 20(12): 3318 - 3327. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Roberts, X. Luo, and N. Chegini Differential regulation of interleukins IL-13 and IL-15 by ovarian steroids, TNF-{alpha} and TGF-{beta} in human endometrial epithelial and stromal cells Mol. Hum. Reprod., October 1, 2005; 11(10): 751 - 760. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Mirkin, M. Arslan, D. Churikov, A. Corica, J.I. Diaz, S. Williams, S. Bocca, and S. Oehninger In search of candidate genes critically expressed in the human endometrium during the window of implantation Hum. Reprod., August 1, 2005; 20(8): 2104 - 2117. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A White and L. A Salamonsen A guide to issues in microarray analysis: application to endometrial biology Reproduction, July 1, 2005; 130(1): 1 - 13. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Dominguez, M. Yanez-Mo, F. Sanchez-Madrid, and C. Simon Embryonic implantation and leukocyte transendothelial migration: different processes with similar players? FASEB J, July 1, 2005; 19(9): 1056 - 1060. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S Bauersachs, S E Ulbrich, K Gross, S E M Schmidt, H H D Meyer, R Einspanier, H Wenigerkind, M Vermehren, H Blum, F Sinowatz, et al. Gene expression profiling of bovine endometrium during the oestrous cycle: detection of molecular pathways involved in functional changes J. Mol. Endocrinol., June 1, 2005; 34(3): 889 - 908. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Escudero, P. J. Boerrigter, H. J. T. C. Bennink, R. Epifanio, J. A. Horcajadas, F. Olivennes, A. Pellicer, and C. Simon Mifepristone Is an Effective Oral Alternative for the Prevention of Premature Luteinizing Hormone Surges and/or Premature Luteinization in Women Undergoing Controlled Ovarian Hyperstimulation for in Vitro Fertilization J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2081 - 2088. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Horcajadas, A. Riesewijk, J. Polman, R. van Os, A. Pellicer, S. Mosselman, and C. Simon Effect of controlled ovarian hyperstimulation in IVF on endometrial gene expression profiles Mol. Hum. Reprod., March 1, 2005; 11(3): 195 - 205. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. P. Ponnampalam, G. C. Weston, A. C. Trajstman, B. Susil, and P. A.W. Rogers Molecular classification of human endometrial cycle stages by transcriptional profiling Mol. Hum. Reprod., December 1, 2004; 10(12): 879 - 893. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Mirkin, G. Nikas, J.-G. Hsiu, J. Diaz, and S. Oehninger Gene Expression Profiles and Structural/Functional Features of the Peri-Implantation Endometrium in Natural and Gonadotropin-Stimulated Cycles J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5742 - 5752. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E.S. Hayes, E.C. Curnow, A.O. Trounson, L.A. Danielson, and E.N. Unemori Implantation and Pregnancy Following In Vitro Fertilization and the Effect of Recombinant Human Relaxin Administration in Macaca fascicularis Biol Reprod, November 1, 2004; 71(5): 1591 - 1597. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
ESHRE Capri Workshop Group Diagnosis and management of the infertile couple: missing information Hum. Reprod. Update, July 1, 2004; 10(4): 295 - 307. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Turksen and T.-C. Troy Barriers built on claudins J. Cell Sci., May 15, 2004; 117(12): 2435 - 2447. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Cervero, J. A. Horcajadas, J. MartIn, A. Pellicer, and C. Simon The Leptin System during Human Endometrial Receptivity and Preimplantation Development J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2442 - 2451. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-Y. Sun, F.-X. Li, J. Li, Y.-F. Tan, Y.-S. Piao, S. Tang, and Y.-L. Wang Determination of Genes Involved in the Early Process of Embryonic Implantation in Rhesus Monkey (Macaca mulatta) by Suppression Subtractive Hybridization Biol Reprod, May 1, 2004; 70(5): 1365 - 1373. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Ahmed, K. M. Brown, D. A. Stephan, J. C. Morrison, E. C. Johnson, and S. I. Tomarev Microarray Analysis of Changes in mRNA Levels in the Rat Retina after Experimental Elevation of Intraocular Pressure Invest. Ophthalmol. Vis. Sci., April 1, 2004; 45(4): 1247 - 1258. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Luna, A. Riesewijk, J. A. Horcajadas, R. d. van Os, F. Dominguez, S. Mosselman, A. Pellicer, and C. Simon Gene expression pattern and immunoreactive protein localization of LGR7 receptor in human endometrium throughout the menstrual cycle Mol. Hum. Reprod., February 1, 2004; 10(2): 85 - 90. [Abstract] [Full Text] [PDF]
|
|