title: Identification of proteins involved in human sperm motility using high-throughput differential proteomics.
abstract: Mammalian sperm motility is a prerequisite for in vivo fertilization, and alterations in this parameter are commonly observed in infertile males. However, we still do not have a complete understanding of the molecular mechanisms controlling it. The aim of this study was to identify proteins involved in human sperm motility deficiency by using TMT protein labeling and LC-MS/MS. Two complementary approaches were used: comparison between sperm samples differing in motility (asthenozoospermic versus normozoospermic) and comparison between sperm subpopulations of fractionated normozoospermic samples differing in motility (non-migrated versus migrated). LC-MS/MS resulted in the identification of 1157 and 887 proteins in the first and second approaches, respectively. Remarkably, similar proteomic alterations were detected in the two experiments, with 80 proteins differentially expressed in the two groups of samples and 93 differentially expressed in the two groups of subpopulations. The differential proteins were analyzed by GO, cellular pathways, and clustering analyses and resulted in the identification of core deregulated proteins and pathways associated with sperm motility dysfunction. These included proteins associated with energetic metabolism, protein folding/degradation, vesicle trafficking, and the cytoskeleton. Contrary to what is usually accepted, the outcomes support the hypothesis that several metabolic pathways (notably, mitochondrial-related ones) contribute toward regulating sperm motility.
authors.affiliation: Human Genetics Research Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Faculty of Medicine, University of Barcelona , Casanova 143, 08036 Barcelona, Spain.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Amaral
authors.forename: Carla
authors.initials: C
authors.lastname: Paiva
authors.forename: Claudio
authors.initials: C
authors.lastname: Attardo Parrinello
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Estanyol
authors.forename: Josep Lluís
authors.initials: JL
authors.lastname: Ballescà
authors.forename: João
authors.initials: J
authors.lastname: Ramalho-Santos
authors.forename: Rafael
authors.initials: R
authors.lastname: Oliva
mesh_terms: D053627:Asthenozoospermia / Q000378:metabolism*; D002853:Chromatography, Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways; D020543:Proteome / Q000032:analysis* / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D012661:Semen / Q000166:cytology / Q000378:metabolism; D013081:Sperm Motility; D013094:Spermatozoa / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: D020543:Proteome
keywords: Human sperm motility; TMT labeling; male infertility; pathways analysis; quantitative proteomics