title: Deregulation of sertoli and leydig cells function in patients with Klinefelter syndrome as evidenced by testis transcriptome analysis.
abstract: BACKGROUND
  Klinefelter Syndrome (KS) is the most common abnormality of sex chromosomes (47,XXY) and represents the first genetic cause of male infertility. Mechanisms leading to KS testis degeneration are still not completely defined but considered to be mainly the result of germ cells loss. In order to unravel the molecular basis of global testis dysfunction in KS patients, we performed a transcriptome analysis on testis biopsies obtained from 6 azoospermic non-mosaic KS patients and 3 control subjects.
  
  
  RESULTS
  The analysis found that, compared to controls, KS patients showed the differential up- and down-expression of 656 and 247 transcripts. The large majority of the deregulated transcripts were expressed by Sertoli cells (SCs) and Leydig cells (LCs). Functional analysis of the deregulated transcripts indicated changes of genes involved in cell death, inflammatory response, lipid metabolism, steroidogenesis, blood-testis-barrier formation and maintenance, as well as spermatogenesis failure.
  
  
  CONCLUSIONS
  Taken together, present data highlight the modulation of hundreds of genes in the somatic components of KS patient testis. The increased LCs steroidogenic function together with the impairment of inflammatory pathways and BTB structure, result in increased apoptosis. These findings may represent a critical roadmap for therapeutic intervention and prevention of KS-related testis failure.
authors: Department of Psychological, Humanities and Territorial Sciences, School of Medicine and Health Sciences, "G.d'Annunzio" University, Via Dei Vestini 31, 66100, Chieti-Pescara, Italy. m.daurora@unich.it.|Functional Genetics Unit, Center of Excellence on Aging (Ce.S.I.), Via Dei Vestini 31, 66100, Chieti, Italy. m.daurora@unich.it.
authors: Marco
authors: M
authors: D'Aurora
authors: Department of Medicine, Section of Endocrinology and Centre for Human Reproduction Pathology, University of Padova, Via Giustiniani 2, 35128, Padova, Italy. alberto.ferlin@unipd.it.
authors: Alberto
authors: A
authors: Ferlin
authors: Department of Sperimental and Clinical Sciences, School of Medicine and Health Sciences, "G.d'Annunzio" University, Via dei Vestini 31, 66100, Chieti-Pescara, Italy. mdinicola@unich.it.
authors: Marta
authors: M
authors: Di Nicola
authors: Department of Medicine, Section of Endocrinology and Centre for Human Reproduction Pathology, University of Padova, Via Giustiniani 2, 35128, Padova, Italy. andrea.garolla@unipd.it.
authors: Andrea
authors: A
authors: Garolla
authors: Department of Medicine, Section of Endocrinology and Centre for Human Reproduction Pathology, University of Padova, Via Giustiniani 2, 35128, Padova, Italy. luca.detoni@unipd.it.
authors: Luca
authors: L
authors: De Toni
authors: Department of Psychological, Humanities and Territorial Sciences, School of Medicine and Health Sciences, "G.d'Annunzio" University, Via Dei Vestini 31, 66100, Chieti-Pescara, Italy. sara.franchi2@virgilio.it.|Functional Genetics Unit, Center of Excellence on Aging (Ce.S.I.), Via Dei Vestini 31, 66100, Chieti, Italy. sara.franchi2@virgilio.it.
authors: Sara
authors: S
authors: Franchi
authors: Department of Oral Health and Biotechnological Sciences, School of Medicine and Health Sciences, "G.d'Annunzio" University, Via dei Vestini 31, 66100, Chieti-Pescara, Italy. gdpalka@unich.it.
authors: Giandomenico
authors: G
authors: Palka
authors: Department of Medicine, Section of Endocrinology and Centre for Human Reproduction Pathology, University of Padova, Via Giustiniani 2, 35128, Padova, Italy. carlo.foresta@unipd.it.
authors: Carlo
authors: C
authors: Foresta
authors: Department of Psychological, Humanities and Territorial Sciences, School of Medicine and Health Sciences, "G.d'Annunzio" University, Via Dei Vestini 31, 66100, Chieti-Pescara, Italy. stuppia@unich.it.|Functional Genetics Unit, Center of Excellence on Aging (Ce.S.I.), Via Dei Vestini 31, 66100, Chieti, Italy. stuppia@unich.it.
authors: Liborio
authors: L
authors: Stuppia
authors: Department of Psychological, Humanities and Territorial Sciences, School of Medicine and Health Sciences, "G.d'Annunzio" University, Via Dei Vestini 31, 66100, Chieti-Pescara, Italy. v.gatta@unich.it.|Functional Genetics Unit, Center of Excellence on Aging (Ce.S.I.), Via Dei Vestini 31, 66100, Chieti, Italy. v.gatta@unich.it.
authors: Valentina
authors: V
authors: Gatta
mesh_terms: D000328:Adult; D001814:Blood-Testis Barrier / Q000378:metabolism; D016000:Cluster Analysis; D015536:Down-Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D007248:Infertility, Male / Q000209:etiology; D059785:Karyotype; D007713:Klinefelter Syndrome / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D007985:Leydig Cells / Q000473:pathology*; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D012708:Sertoli Cells / Q000473:pathology*; D012730:Sex Chromosomes; D015398:Signal Transduction; D013091:Spermatogenesis / Q000235:genetics; D013737:Testis / Q000378:metabolism*; D059467:Transcriptome; D015854:Up-Regulation