title: MicroRNAs are associated with human embryo implantation defects.
abstract: BACKGROUND
  Repeated implantation failure (RIF) is a major problem encountered in IVF. We have previously reported that RIF-IVF patients have a different endometrial gene expression profile during the window of implantation. Considering microRNA (miRNA) function in post-transcriptional regulation of gene expression, the aim of the study was to evaluate the involvement of miRNA in defects of endometrial receptivity.
  
  
  METHODS
  We used TaqMan miRNA array cards to identify the miRNAs differentially expressed in the secretory endometrium of RIF-IVF patients when compared with fertile women, and bioinformatics tools to identify their predicted targets and the molecular networks they may affect.
  
  
  RESULTS
  Comparing miRNA expression profiles, we identified 13 miRNAs, differentially expressed in RIF endometrial samples, that putatively regulate the expression of 3800 genes. We found that 10 miRNAs were overexpressed (including miR 145, 23b and 99a) and 3 were underexpressed. Using our previous gene expression analysis, we paralleled miRNA-mRNA expression profiling. By this means, we identified novel and previously characterized miRNA-regulated molecular pathways such as adherens junctions, cell adhesion molecules, Wnt-signaling, p53 signaling and cell cycle pathways. Consistent with the miRNA-predicted targets, mRNA levels of N-cadherin, H2AFX, netrin-4 and secreted frizzled-related protein-4, belonging to the cell adhesion molecules, Wnt signaling and cell cycle pathways were lower in RIF-IVF patients.
  
  
  CONCLUSIONS
  To our knowledge, this is the first study to evaluate the differential expression of miRNAs in the secretory endometrium of RIF-IVF patients. We suggest that the RIF-associated miRNAs could be exploited as new candidates for diagnosis and treatment of embryo implantation failures.
authors.affiliation: Department of Obstetrics and Gynecology, Hadassah University Hospital, Jerusalem 91120, Israel.
authors.forename: Ariel
authors.initials: A
authors.lastname: Revel
authors.forename: Hanna
authors.initials: H
authors.lastname: Achache
authors.forename: Juliet
authors.initials: J
authors.lastname: Stevens
authors.forename: Yoav
authors.initials: Y
authors.lastname: Smith
authors.forename: Reuven
authors.initials: R
authors.lastname: Reich
mesh_terms: D000328:Adult; D015820:Cadherins / Q000096:biosynthesis; D002448:Cell Adhesion; D002453:Cell Cycle; D010064:Embryo Implantation; D004717:Endometrium / Q000378:metabolism / Q000473:pathology; D005260:Female; D005307:Fertilization in Vitro / Q000379:methods*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006657:Histones / Q000096:biosynthesis; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000096:biosynthesis; D000075385:Netrins; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D012313:RNA / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D015820:Cadherins; D006657:Histones; D035683:MicroRNAs; D009414:Nerve Growth Factors; D000075385:Netrins; D011518:Proto-Oncogene Proteins; D012313:RNA; D016159:Tumor Suppressor Protein p53; C468783:H2AX protein, human; C541010:MIRN145 microRNA, human; C552430:MIRN23a microRNA, human; C498815:NTN4 protein, human; C118723:SFRP4 protein, human; D000094742:Secreted Frizzled-Related Proteins; C495901:TP53 protein, human