Unbiased label-free quantitative proteomic profiling and enriched proteomic pathways in seminal plasma of adult men before and after varicocelectomy

Unbiased label-free quantitative proteomic profiling and enriched proteomic pathways in seminal plasma of adult men before and after varicocelectomy

Author Camargo, M. Autor UNIFESP Google Scholar
Intasqui Lopes, P. Autor UNIFESP Google Scholar
Del Giudice, P. T. Autor UNIFESP Google Scholar
Carvalho, V. M. Google Scholar
Cardozo, K. H. M. Google Scholar
Andreoni, C. Autor UNIFESP Google Scholar
Fraietta, Renato Autor UNIFESP Google Scholar
Bertolla, Ricardo Pimenta Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Fleury Grp
Abstract STUDY QUESTION: Does the seminal plasma proteomic profile and functional enrichment of gene ontology terms change after microsurgical varicocelectomy? Are there any potential targets for diagnosis or therapeutic intervention in varicocele?SUMMARY ANSWER: A shift in state from a responsive-to-stress condition before varicocele correction to a responsive-to-environment condition after varicocelectomy was observed in enriched proteomic pathways.WHAT IS KNOWN ALREADY: Varicocele may lead to many adverse effects, including failure of testicular growth and development, and is associated with decreased semen quality and increased semen oxidative stress. Varicocelectomy is the treatment of choice, and is associated with improved semen quality, but little is known regarding the underlying molecular mechanisms and post-genomic pathways following intervention.STUDY DESIGN, SIZE, DURATION: A prospective study was carried out including 18 adult men with varicocele. These patients provided one semen sample before they were submitted for bilateral varicocele repair through microsurgical varicocelectomy, and one other semen sample 90 days after the surgery.PARTICIPANTS/MATERIALS, SETTING, METHODS: An aliquot of each semen sample was used for unbiased proteomics analysis by a label-free quantitative approach (2D nanoUPLC-ESI-MSE). Samples were pooled according to group (normalized to protein content) and run in quadruplicate. These quadruplicate runs provided degrees of freedom in order to compare groups using a non-parametric Mann-Whitney test for quantified proteins.MAIN RESULTS and the ROLE of CHANCE: A total of 316 proteins were quantified or identified, of which 91 were exclusively identified or quantified in one of the groups (53 in the pre- and 38 in the post-varicocelectomy group), and 68 were quantified in both groups and submitted to statistical analysis, of which 5 were overrepresented in the pre-varicocelectomy group (P < 0.05). in enriched functional analysis, binding and response to stimulus functions were enriched in a common cluster (present in both groups), nitric oxide metabolism and tetratricopeptide repeat domain-binding functions were enriched in the pre-varicocelectomy group, and response to reactive oxygen species, gluconeogenesis, nicotinamide adenine dinucleotide-binding and protein stabilization were enriched in the post-varicocelectomy.LIMITATIONS, REASONS for CAUTION: Because a shotgun proteomics analysis was chosen in order to generate a list of putative biomarkers, a targeted follow-up study should be performed to confirm these biomarkers.WIDER IMPLICATIONS of the FINDINGS: the proteins found in both groups possess functions usually found in human semen. the enriched function analysis demonstrated a shift back to homeostasis after varicocelectomy, suggesting that varicocele correction promotes return of semen to a physiological state.
Keywords male infertility
varicocele
varicocelectomy
seminal plasma
proteomics
Language English
Sponsor Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Date 2013-01-01
Published in Human Reproduction. Oxford: Oxford Univ Press, v. 28, n. 1, p. 33-46, 2013.
ISSN 0268-1161 (Sherpa/Romeo, impact factor)
Publisher Oxford Univ Press
Extent 33-46
Origin http://dx.doi.org/10.1093/humrep/des357
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000313834400006
URI http://repositorio.unifesp.br/handle/11600/35663

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