title: Quantitative proteomic analysis of human testis reveals system-wide molecular and cellular pathways associated with non-obstructive azoospermia.
abstract: Male infertility accounts for half of the infertility problems experienced by couples. Azoospermia, having no measurable level of sperm in seminal fluid, is one of the known conditions resulting in male infertility. In order to elucidate the complex molecular mechanisms causing male azoospermia, label-free quantitative shotgun proteomics was carried out on testicular tissue specimens from patients with obstructive azoospermia and non-obstructive azoospermia, including maturation arrest (MA) and Sertoli cell only syndrome (SCOS). The abundance of 520 proteins was significantly changed across three groups of samples. We were able to identify several functional biological pathways enriched in azoospermia samples and confirm selected differentially abundant proteins, using multiple histological methods. The results revealed that cell cycle and proteolysis, and RNA splicing were the most significant biological processes impaired by the substantial suppression of proteins related to the aforementioned categories in SCOS tissues. In the MA patient testes, generation of precursor metabolites and energy as well as oxidation-reduction were the most significantly altered processes. Novel candidate proteins identified in this study include key transcription factors, many of which have not previously been shown to be associated with azoospermia. Our findings can provide substantial insights into the molecular regulation of spermatogenesis and human reproduction.
  
  
  
  The obtained data showed a drastic suppression of proteins involved in spliceosome, cell cycle and proteasome proteins, as well as energy and metabolic production in Sertoli cell only syndrome testis tissue, and to a lesser extent in maturation arrest samples. Moreover, we identified new transcription factors that are highly down-regulated in SCOS and MA patients, thus helping to understand the molecular complexity of spermatogenesis in male infertility. Our findings provide novel candidate protein targets associated with SCOS or MA azoospermia.
authors.affiliation: Department of Molecular Systems Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Alikhani
authors.affiliation: Department of Chemistry and Biomolecular Sciences, Macquarie University, North Ryde, New South Wales, Australia.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Mirzaei
authors.affiliation: Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
authors.forename: Marjan
authors.initials: M
authors.lastname: Sabbaghian
authors.affiliation: Department of Molecular Systems Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
authors.forename: Pouria
authors.initials: P
authors.lastname: Parsamatin
authors.affiliation: Department of Molecular Systems Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
authors.forename: Razieh
authors.initials: R
authors.lastname: Karamzadeh
authors.affiliation: Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
authors.forename: Samane
authors.initials: S
authors.lastname: Adib
authors.affiliation: Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
authors.forename: Niloofar
authors.initials: N
authors.lastname: Sodeifi
authors.affiliation: Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
authors.forename: Mohammad Ali Sadighi
authors.initials: MAS
authors.lastname: Gilani
authors.affiliation: Center for Biotechnology and Genomics, Texas Tech University, Lubbock, TX, United States.
authors.forename: Masoud
authors.initials: M
authors.lastname: Zabet-Moghaddam
authors.affiliation: Department of Chemistry and Biomolecular Sciences, Macquarie University, North Ryde, New South Wales, Australia; ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), Macquarie University, North Ryde, New South Wales, Sydney, Australia.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Parker
authors.affiliation: Department of Chemistry and Biomolecular Sciences, Macquarie University, North Ryde, New South Wales, Australia.
authors.forename: Yunqi
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Faculty of Medicine and Health Sciences, Macquarie University, NSW 2109, Australia.
authors.forename: Vivek
authors.initials: V
authors.lastname: Gupta
authors.affiliation: Department of Chemistry and Biomolecular Sciences, Macquarie University, North Ryde, New South Wales, Australia.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Haynes
authors.affiliation: Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Gourabi
authors.affiliation: Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Department of Developmental Biology, University of Science and Culture, Tehran, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Baharvand
authors.affiliation: Department of Molecular Systems Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Agricultural Biotechnology Research Institute of Iran, Karaj, Tehran, Iran. Electronic address: salekdeh@royaninstitute.org.
authors.forename: Ghasem Hosseini
authors.initials: GH
authors.lastname: Salekdeh
mesh_terms: D053713:Azoospermia / Q000209:etiology*; D006801:Humans; D007248:Infertility, Male / Q000209:etiology; D008297:Male; D053858:Metabolic Networks and Pathways; D059748:Proteolysis; D040901:Proteomics / Q000379:methods*; D012326:RNA Splicing; D054331:Sertoli Cell-Only Syndrome; D013737:Testis / Q000737:chemistry / Q000378:metabolism*
keywords: Azoospermia; Infertility; Label-free quantitation; Maturation arrest; Sertoli cell only syndrome; Shotgun proteomics; Testis