title: Transcriptomic changes during the pre-receptive to receptive transition in human endometrium detected by RNA-Seq.
abstract: BACKGROUND
  Identifying novel molecular markers for assessing endometrial receptivity is necessary for understanding human implantation and may help in improving the clinical outcome of in vitro fertilization.
  
  
  OBJECTIVE
  We aimed to compare the gene expression profiles of the pre-receptive vs receptive phases of the natural cycle in human endometrial biopsies.
  
  
  METHODS
  The design of this study was detecting the global gene expression profile of human endometrial receptivity by RNA-Seq.
  
  
  METHODS
  This study was conducted at a university reproductive center.
  
  
  METHODS
  Twelve women with normal menstrual cycles participated in the study.
  
  
  METHODS
  Study interventions included endometrial biopsies.
  
  
  METHODS
  The endometrial transcriptomes were determined by RNA-Seq, and the expression of selected differentially expressed genes (DEGs) was validated by quantitative RT-PCR.
  
  
  RESULTS
  A total of 2372 DEGs were identified by RNA-Seq. Of these genes, 1099 were up-regulated at LH+7 versus LH+2, whereas 1273 were down-regulated. Nineteen selected genes were confirmed by quantitative RT-PCR. We first demonstrated that metallothionein (MT) family members, MT1E, F, G, H, M, X, and 2A, and four novel transcripts, HAP1, ZCCHC12, MRAP2, and OVGP1, which were not previously linked to endometrial physiology, showed significant expression changes during implantation. Mineral absorption was the most enriched pathway for up-regulated genes, and cell cycle was enriched for down-regulated genes. Gene co-expression network analysis identified five core regulatory factors (GLI2, CDC25A, TLR9, MT1G, and SLC5A1) that are involved in endometrial receptivity during implantation. Examination of the promoter regions of the DEGs identified AP2 and SP1 binding sites, suggesting a potential regulatory role in endometrial gene expression for these two transcription factors.
  
  
  CONCLUSIONS
  This study provides the first RNA-Seq-based transcriptome comparison of pre-receptive and receptive human endometria. Many novel candidate genes, which have not been previously studied in human endometrium, may have functional significance during implantation and serve as molecular markers for endometrial receptivity.
authors.affiliation: Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics (S.G.H., Y.W., H.J.X., X.W.J., Y.Q.H., Q.L.Z., Z.J.C., Y.S.), Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, China; Shanghai Key Laboratory for Molecular Andrology (S.G.H., G.X.Y.), State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Shuanggang
authors.initials: S
authors.lastname: Hu
authors.forename: Guangxin
authors.initials: G
authors.lastname: Yao
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Haijing
authors.initials: H
authors.lastname: Xu
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Ji
authors.forename: Yaqiong
authors.initials: Y
authors.lastname: He
authors.forename: Qinling
authors.initials: Q
authors.lastname: Zhu
authors.forename: Zijiang
authors.initials: Z
authors.lastname: Chen
authors.forename: Yun
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000328:Adult; D002453:Cell Cycle; D004717:Endometrium / Q000378:metabolism* / Q000502:physiology*; D005260:Female; D015870:Gene Expression / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008903:Minerals / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis* / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods*; D014157:Transcription Factors / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics*
chemical_list: D008903:Minerals; D014157:Transcription Factors; D012313:RNA; D007986:Luteinizing Hormone