title: Global human tissue profiling and protein network analysis reveals distinct levels of transcriptional germline-specificity and identifies target genes for male infertility.
abstract: BACKGROUND
  Mammalian spermatogenesis is a process that involves a complex expression program in both somatic and germ cells present in the male gonad. A number of studies have attempted to define the transcriptome of male meiosis and gametogenesis in rodents and primates. Few human transcripts, however, have been associated with testicular somatic cells and germ cells at different post-natal developmental stages and little is known about their level of germline-specificity compared with non-testicular tissues.
  
  
  METHODS
  We quantified human transcripts using GeneChips and a total of 47 biopsies from prepubertal children diagnosed with undescended testis, infertile adult patients whose spermatogenesis is arrested at consecutive stages and fertile control individuals. These results were integrated with data from enriched normal germ cells, non-testicular expression data, phenotype information, predicted regulatory DNA-binding motifs and interactome data.
  
  
  RESULTS
  Among 3580 genes for which we found differential transcript concentrations in somatic and germ cells present in human testis, 933 were undetectable in 45 embryonic and adult non-testicular tissues, including many that were corroborated at protein level by published gene annotation data and histological high-throughput protein immunodetection assays. Using motif enrichment analyses, we identified regulatory promoter elements likely involved in germline development. Finally, we constructed a regulatory disease network for human fertility by integrating expression signals, interactome information, phenotypes and functional annotation data.
  
  
  CONCLUSIONS
  Our results provide broad insight into the post-natal human testicular transcriptome at the level of cell populations and in a global somatic tissular context. Furthermore, they yield clues for genetic causes of male infertility and will facilitate the identification of novel cancer/testis genes as targets for cancer immunotherapies.
authors.affiliation: Inserm Unit 1085-IRSET,  Université de Rennes 1,  EHESP School of Public Health, F-35042 Rennes,  France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Chalmel
authors.forename: Aurélie
authors.initials: A
authors.lastname: Lardenois
authors.forename: Bertrand
authors.initials: B
authors.lastname: Evrard
authors.forename: Romain
authors.initials: R
authors.lastname: Mathieu
authors.forename: Caroline
authors.initials: C
authors.lastname: Feig
authors.forename: Philippe
authors.initials: P
authors.lastname: Demougin
authors.forename: Alexandre
authors.initials: A
authors.lastname: Gattiker
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schulze
authors.forename: Bernard
authors.initials: B
authors.lastname: Jégou
authors.forename: Christiane
authors.initials: C
authors.lastname: Kirchhoff
authors.forename: Michael
authors.initials: M
authors.lastname: Primig
mesh_terms: D000328:Adult; D020816:Amino Acid Motifs; D000818:Animals; D002648:Child; D003456:Cryptorchidism / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007248:Infertility, Male / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D020543:Proteome / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013045:Species Specificity; D013091:Spermatogenesis; D013737:Testis / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; D020543:Proteome; D012333:RNA, Messenger