Quantitative proteomic analysis of human testis reveals system-wide molecular and cellular pathways associated with non-obstructive azoospermia
Autor: | Samane Adib, Razieh Karamzadeh, Hossein Baharvand, Masoud Zabet-Moghaddam, Hamid Gourabi, Mehdi Mirzaei, Ghasem Hosseini Salekdeh, Paul A. Haynes, Mohammad Ali Sadighi Gilani, Niloofar Sodeifi, Marjan Sabbaghian, Yunqi Wu, Vivek Gupta, Pouria Parsamatin, Mehdi Alikhani, Lindsay M. Parker |
---|---|
Rok vydání: | 2017 |
Předmět: |
Male
Proteomics 0301 basic medicine Infertility endocrine system medicine.medical_specialty RNA Splicing Biophysics Obstructive azoospermia Biology Biochemistry Male infertility Sertoli cell-only syndrome 03 medical and health sciences 0302 clinical medicine Internal medicine Testis medicine Humans Shotgun proteomics Transcription factor Infertility Male Azoospermia 030219 obstetrics & reproductive medicine Sertoli Cell-Only Syndrome Cell cycle medicine.disease Cell biology 030104 developmental biology Endocrinology Proteolysis Metabolic Networks and Pathways |
Zdroj: | Journal of Proteomics. 162:141-154 |
ISSN: | 1874-3919 |
Popis: | 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. Significance 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. |
Databáze: | OpenAIRE |
Externí odkaz: |