title: Identification of genital tract markers in the human seminal plasma using an integrative genomics approach.
abstract: OBJECTIVE
  Can protein biomarkers of the male genital tract be identified in human seminal plasma?
  
  
  CONCLUSIONS
  We identified potential biomarkers for each of the organs participating in the secretions of the human seminal plasma.
  
  
  BACKGROUND
  The seminal plasma fulfills critical functions for fertility by providing spermatozoa with a protective milieu, promoting their final maturation and modulating the immune responsiveness of the female reproductive tract. It is also considered to be a promising source of biomarkers of male infertility and/or pathologies of the male genital tract.
  
  
  METHODS
  This study combines proteomic analyses of normal seminal plasma together with transcriptomic gene expression profiling of human healthy tissues.
  
  
  METHODS
  Non-liquefied seminal plasma proteins from a healthy donor were prefractionated using two sequential Proteominer™ libraries. Eight subproteome fractions were collected, trypsin digested and subjected to three successive mass spectrometry analyses for peptide characterization. The list of identified proteins was compared with and merged with other available data sets of the human seminal plasma proteome. The expression of corresponding genes was then investigated using tissue transcriptome profiles to determine where, along the male reproductive tract, these proteins were produced. Finally, tissue specificity of a selected subset of biomarker candidates was validated on human tissues.
  
  
  RESULTS
  We first performed a proteomic analysis of the human seminal plasma and identified 699 proteins. By comparing our protein list with other previous proteomic data sets, we found that 2545 unique proteins have been described so far in the human seminal plasma. We then profiled their expression at the gene level and identified 83 testis, 42 epididymis, 7 seminal vesicle and 17 prostate candidate protein markers. For a subset of testis-specific candidates, i.e. TKTL1, LDHC and PGK2, we further validated their germ cell expression and demonstrated that such markers could distinguish between semen from fertile and infertile men.
  
  
  CONCLUSIONS
  While some of the markers we identified are well-known tissue-specific products, further dedicated studies to validate the biomarker status of new candidates will be required. Additionally, whether or not the abundance of these proteins is indeed decreased in some specific pathological situations remains to be determined.
  
  
  CONCLUSIONS
  Using an integrative genomics approach, we identified biomarker candidates for each of the organs participating in the seminal plasma production. In this study, we essentially focused on germ cell markers and their potential application for the diagnosis of male infertility. Other types of markers also deserve a focused attention given their potential predictive value for various reproductive disorders, notably for prostate cancers.
  
  
  BACKGROUND
  This work was supported by the Proteomics Core Facility at Biogenouest and was funded by Conseil Régional de Bretagne, IBiSA and Agence de la Biomédecine grants. The authors declare that there exists a competing financial interest in this work that is related to a patent application on the use of identified germ cell-specific proteins in an antibody-based assay (Fertichip™) to predict the successful testicular biopsy outcomes in human non-obstructive azoospermia.
authors.affiliation: Inserm, U1085, IRSET, University of Rennes I, Campus de Beaulieu, Rennes cedex F-35042, France.
authors.forename: A D
authors.initials: AD
authors.lastname: Rolland
authors.forename: R
authors.initials: R
authors.lastname: Lavigne
authors.forename: C
authors.initials: C
authors.lastname: Dauly
authors.forename: P
authors.initials: P
authors.lastname: Calvel
authors.forename: C
authors.initials: C
authors.lastname: Kervarrec
authors.forename: T
authors.initials: T
authors.lastname: Freour
authors.forename: B
authors.initials: B
authors.lastname: Evrard
authors.forename: N
authors.initials: N
authors.lastname: Rioux-Leclercq
authors.forename: J
authors.initials: J
authors.lastname: Auger
authors.forename: C
authors.initials: C
authors.lastname: Pineau
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D020869:Gene Expression Profiling; D005832:Genital Diseases, Male / Q000378:metabolism*; D005837:Genitalia, Male / Q000378:metabolism*; D023281:Genomics / Q000379:methods; D006801:Humans; D007248:Infertility, Male / Q000378:metabolism*; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008297:Male; D009928:Organ Specificity; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010449:Peptide Mapping; D010735:Phosphoglycerate Kinase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012661:Semen / Q000378:metabolism*; D029589:Seminal Plasma Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013094:Spermatozoa / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D014174:Transketolase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D007527:Isoenzymes; D010446:Peptide Fragments; D029589:Seminal Plasma Proteins; D007770:L-Lactate Dehydrogenase; C409673:lactate dehydrogenase C4; C505431:TKTL1 protein, human; D014174:Transketolase; D010735:Phosphoglycerate Kinase; C104317:phosphoglycerate kinase, testis specific