title: Deciphering the proteomic signature of human endometrial receptivity.
abstract: OBJECTIVE
  Are there any proteomic differences between receptive (R) and non-receptive (NR) endometrial receptivity array (ERA)-diagnosed endometria obtained on the same day of a hormonal replacement therapy (HRT) treatment cycle?
  
  
  CONCLUSIONS
  There is a different proteomic signature between R and NR ERA-diagnosed endometrium obtained on the same day of HRT cycles.
  
  
  BACKGROUND
  The human endometrial transcriptome has been extensively investigated in the last decade resulting in the development of a new diagnostic test based on the transcriptomic signature of the window of implantation (WOI). Much less is known about the proteomics derived from the transcripts present during the WOI.
  
  
  METHODS
  This study was a basic proteomic analysis of human endometrial biopsies taken from twelve IVF patients.
  
  
  METHODS
  Human endometrial biopsies were collected during HRT cycles after 5 days of progesterone (P) administration, and diagnosed as receptive (R; n = 6) or non-receptive (NR; n = 6) by the ERA test. Endometrial proteins were extracted, labelled and separated using differential in-gel electrophoresis (DIGE). Proteins were identified using mass spectrometry, followed up by in silico analysis. Validation studies using western blots and immunolocalization were performed for the progesterone receptor membrane component 1 (PGRMC1) and annexin A6 (ANXA6) proteins.
  
  
  RESULTS
  DIGE analysis followed by protein identification by MALDI-MS and database searches revealed 24 differentially expressed proteins in R versus NR samples. In silico analysis showed two pathways which were significantly different between R and NR samples. Expression of PGRMC1 and ANXA6 was validated and localized by western blots and immunohistochemistry. These results highlight these proteins as key targets likely to be important in the comprehension of human endometrial receptivity.
  
  
  CONCLUSIONS
  This was mainly a descriptive study with no functional studies on the proteins found. We also used a low number of human endometrial samples for the DIGE analysis.
  
  
  CONCLUSIONS
  This study identified the proteomic profile associated with receptive or non-receptive human endometria. Our findings suggest that although histological dating indicates a putative 'receptive' status within the WOI, a different transcriptomic and proteomic profile is observed in these samples. We should move towards using more personalized WOIs, where identification of the correct endometrial receptivity status, and consequently the success of IVF, relies on individual molecular signatures rather than traditional endometrial dating.
  
  
  BACKGROUND
  F.D.'s participation in this work was supported by the Spanish Ministry of Economy and Competitiveness, through the Miguel Servet Programme (CP13/00075) co-founded by FEDER. The project was also supported by a grant from the Spanish Ministry of Economy and Competitiveness, through the FIS Programme (PI12/00450). The authors have no financial/commercial conflicts of interest to declare.
authors.affiliation: Fundación Instituto Valenciano de Infertilidad (FIVI), Instituto Universitario IVI (IUIVI), Valencia, Spain INCLIVA Biomedical Research Institute, Valencia, Spain.
authors.forename: Tamara
authors.initials: T
authors.lastname: Garrido-Gómez
authors.affiliation: Fundación Instituto Valenciano de Infertilidad (FIVI), Instituto Universitario IVI (IUIVI), Valencia, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Quiñonero
authors.affiliation: Proteomics Unit, Valencia University, Valencia, Spain.
authors.forename: Oreto
authors.initials: O
authors.lastname: Antúnez
authors.affiliation: Fundación Instituto Valenciano de Infertilidad (FIVI), Instituto Universitario IVI (IUIVI), Valencia, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Díaz-Gimeno
authors.affiliation: Fundación Instituto Valenciano de Infertilidad (FIVI), Instituto Universitario IVI (IUIVI), Valencia, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Bellver
authors.affiliation: Fundación Instituto Valenciano de Infertilidad (FIVI), Instituto Universitario IVI (IUIVI), Valencia, Spain Department of Pediatrics, Obstetrics and Gynecology, Valencia University, INCLIVA, Valencia, Spain Department of Obstetrics and Gynecology, Stanford University, Stanford, CA, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Simón
authors.affiliation: Fundación Instituto Valenciano de Infertilidad (FIVI), Instituto Universitario IVI (IUIVI), Valencia, Spain INCLIVA Biomedical Research Institute, Valencia, Spain francisco.dominguez@ivi.es.
authors.forename: Francisco
authors.initials: F
authors.lastname: Domínguez
mesh_terms: D017317:Annexin A6 / Q000032:analysis / Q000378:metabolism; D010064:Embryo Implantation; D004717:Endometrium / Q000378:metabolism / Q000502:physiology*; D005260:Female; D005307:Fertilization in Vitro; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D013058:Mass Spectrometry; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism; D011374:Progesterone / Q000627:therapeutic use; D020543:Proteome; D040901:Proteomics; D011980:Receptors, Progesterone / Q000032:analysis / Q000378:metabolism
chemical_list: D017317:Annexin A6; D008565:Membrane Proteins; C115296:PGRMC1 protein, human; D020543:Proteome; D011980:Receptors, Progesterone; D011374:Progesterone
keywords: PGRMC1; annexin A6; endometrium; proteomics; receptivity