Meritxell Jodar1, Claudio Attardo-Parrinello1, Ada Soler-Ventura1, Ferran Barrachina1, David Delgado-Dueñas1, Salvadora Cívico2, Josep Maria Calafell2, Josep Lluís Ballescà2, Rafael Oliva3. 1. EUGIN-UB Research Excellence Program; Molecular Biology of Reproduction and Development Research Group, Fundació Clínic per a la Recerca Biomèdica (FCRB), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, Casanova 143, Barcelona 08036, Spain. 2. EUGIN-UB Research Excellence Program; Clinic Institute of Gynaecology, Obstetrics and Neonatology (ICGON), Hospital Clínic, Villarroel 170, Barcelona, Spain. 3. EUGIN-UB Research Excellence Program; Molecular Biology of Reproduction and Development Research Group, Fundació Clínic per a la Recerca Biomèdica (FCRB), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, Casanova 143, Barcelona 08036, Spain; Biochemistry and Molecular Genetics Service, Hospital Clínic, Villarroel 170, Barcelona 08036, Spain. Electronic address: roliva@ub.edu.
Abstract
RESEARCH QUESTION: Do alterations of human sperm protein profile affect embryo quality? DESIGN: Sperm proteins from 27 infertile couples undergoing intracytoplasmic sperm injection (ICSI) were extracted and digested. The resulting peptides were labelled using tandem mass tags, separated by two-dimensional liquid chromatography, and identified and quantified using tandem mass spectrometry. Subsequently, sperm protein and peptide abundance were statistically analysed for correlation with ICSI-derived embryo quality in the subset of idiopathic infertile couples. Detected correlations were further assessed in the subset of infertile patients with a known factor. RESULTS: The abundance of 18 individual sperm proteins was found to correlate with embryo quality after ICSI. Of note, a high percentage of poor-quality ICSI-derived embryos was associated with alterations in several components of the eight-membered chaperonin-containing T-complex, which plays an important role in the folding of many essential proteins. Additionally, the abundance of sperm proteins with known functions in embryogenesis, such as RUBVL1, also correlated with early embryo quality (r = -0.547; P = 0.028). Some of the correlations found in this study were validated using either proteomic data from infertile patients with a known factor or data from similar published studies. Analysis at the peptide level revealed the association of some correlations with specific post-translational modifications or isoforms. CONCLUSIONS: Our results support the hypothesis that the sperm proteome plays a role in early embryogenesis. Moreover, several sperm proteins have emerged as potential biomarkers that could predict the outcome of in-vitro assisted reproductive technologies, leading to the possibility of improved diagnosis of couples with idiopathic infertility.
RESEARCH QUESTION: Do alterations of human sperm protein profile affect embryo quality? DESIGN: Sperm proteins from 27 infertile couples undergoing intracytoplasmic sperm injection (ICSI) were extracted and digested. The resulting peptides were labelled using tandem mass tags, separated by two-dimensional liquid chromatography, and identified and quantified using tandem mass spectrometry. Subsequently, sperm protein and peptide abundance were statistically analysed for correlation with ICSI-derived embryo quality in the subset of idiopathic infertile couples. Detected correlations were further assessed in the subset of infertilepatients with a known factor. RESULTS: The abundance of 18 individual sperm proteins was found to correlate with embryo quality after ICSI. Of note, a high percentage of poor-quality ICSI-derived embryos was associated with alterations in several components of the eight-membered chaperonin-containing T-complex, which plays an important role in the folding of many essential proteins. Additionally, the abundance of sperm proteins with known functions in embryogenesis, such as RUBVL1, also correlated with early embryo quality (r = -0.547; P = 0.028). Some of the correlations found in this study were validated using either proteomic data from infertilepatients with a known factor or data from similar published studies. Analysis at the peptide level revealed the association of some correlations with specific post-translational modifications or isoforms. CONCLUSIONS: Our results support the hypothesis that the sperm proteome plays a role in early embryogenesis. Moreover, several sperm proteins have emerged as potential biomarkers that could predict the outcome of in-vitro assisted reproductive technologies, leading to the possibility of improved diagnosis of couples with idiopathic infertility.