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Human sperm phosphoproteome reveals differential phosphoprotein signatures that regulate human sperm motility.
J Proteomics 2020; 215:103654JP

Abstract

Human sperm motility is essential for fertilization and among pathologies underlying male infertility is asthenozoospermia. Nevertheless, mechanisms regulating sperm motility are not completely unraveled. This work investigates phosphoproteins underlying human sperm motility by using differential phosphoproteomic in two human sperm subpopulations: high (HM) and low (LM) motility, obtained by centrifugation in a density gradient. Phosphoproteomics (HPLC-MS/MS triple TOF), comparing human LM and HM phosphoproteomes, identified 210 phosphopeptides with different abundance that correspond with 119 sperm proteins. Analysis showed that 40% of phosphoproteins in LM spermatozoa are involved in metabolism, (catabolism, protein transport, lipid biosynthesis), 25% in spermatogenesis and sperm function, 8% in immune system and 6% in DNA repair. In HM spermatozoa, 48% of phosphoproteins are related to spermatogenesis and sperm function (motility), whereas 8% are associated to metabolism. GSK3α resulted one of the most abundant phosphoproteins in HM spermatozoa. Western blot confirmed that GSK3α phosphorylation is higher in HM spermatozoa. Summarizing, this study i) identified phosphoproteins in two human spermatozoa populations, ii) supports that human spermatozoa rely in protein phosphorylation, such as GSK3 α, to regulate sperm motility, iv) raises the challenge of using some identified human sperm phosphorylated proteins (GSK3α) as targets to develop into clinically relevant biomarkers.

SIGNIFICANCE:

Human sperm phosphoproteome analyzed by nano HPLC-MS/MS triple TOF identifies the differential abundance of sperm phosphoproteins in two human sperm populations exhibiting high motility (HM) and/or low motility (LM) that were isolated from normozoospermic healthy donors. Majority of human phosphoproteins found in LM spermatozoa are involved in sperm metabolism (40%), whereas those in HM spermatozoa are associated to spermatogenesis and sperm function, as motility (48%), and only 8% are associated to metabolism. One of the most abundant phosphoproteins found in HM spermatozoa is GSK3α, kinase directly involved in the regulation of sperm motility that was also validated by western blot. The biological relevance of this study is based in the fact that supports that mature human sperm cells rely in protein phosphorylation to efficiently regulate sperm motility and allows identifying those regulatory human sperm phosphoproteins. This work will clearly impacts the human reproductive field as it raises the challenge of consider identified human sperm phosphoproteins, such as GSK3α, as potential biological targets to develop into relevant biomarkers for the human clinic or assisted reproductive technology.

Authors+Show Affiliations

Research Group of Intracellular Signalling and Technology of Reproduction (SINTREP), Institute of Biotechnology in Agriculture and Livestock (INBIO G+C), University of Extremadura, Caceres, Spain; Unit for Multidisciplinary Research in Biomedicine (UMIB), Laboratory of Cell Biology, Department of Microscopy, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.Research Group of Intracellular Signalling and Technology of Reproduction (SINTREP), Institute of Biotechnology in Agriculture and Livestock (INBIO G+C), University of Extremadura, Caceres, Spain.Department of Medicine and Animal Health, University of Extremadura, Caceres, Spain.Research Group of Intracellular Signalling and Technology of Reproduction (SINTREP), Institute of Biotechnology in Agriculture and Livestock (INBIO G+C), University of Extremadura, Caceres, Spain.Research Group of Intracellular Signalling and Technology of Reproduction (SINTREP), Institute of Biotechnology in Agriculture and Livestock (INBIO G+C), University of Extremadura, Caceres, Spain. Electronic address: jbragado@unex.es.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31972345

Citation

Martin-Hidalgo, David, et al. "Human Sperm Phosphoproteome Reveals Differential Phosphoprotein Signatures That Regulate Human Sperm Motility." Journal of Proteomics, vol. 215, 2020, p. 103654.
Martin-Hidalgo D, Serrano R, Zaragoza C, et al. Human sperm phosphoproteome reveals differential phosphoprotein signatures that regulate human sperm motility. J Proteomics. 2020;215:103654.
Martin-Hidalgo, D., Serrano, R., Zaragoza, C., Garcia-Marin, L. J., & Bragado, M. J. (2020). Human sperm phosphoproteome reveals differential phosphoprotein signatures that regulate human sperm motility. Journal of Proteomics, 215, p. 103654. doi:10.1016/j.jprot.2020.103654.
Martin-Hidalgo D, et al. Human Sperm Phosphoproteome Reveals Differential Phosphoprotein Signatures That Regulate Human Sperm Motility. J Proteomics. 2020 Jan 20;215:103654. PubMed PMID: 31972345.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human sperm phosphoproteome reveals differential phosphoprotein signatures that regulate human sperm motility. AU - Martin-Hidalgo,David, AU - Serrano,Rebeca, AU - Zaragoza,Concepcion, AU - Garcia-Marin,Luis J, AU - Bragado,M Julia, Y1 - 2020/01/20/ PY - 2019/10/29/received PY - 2020/01/09/revised PY - 2020/01/18/accepted PY - 2020/1/24/pubmed PY - 2020/1/24/medline PY - 2020/1/24/entrez KW - Glycogen shynthase kinase 3α KW - Human spermatozoa KW - Motility KW - Phosphoproteomic KW - Protein phosphorylation SP - 103654 EP - 103654 JF - Journal of proteomics JO - J Proteomics VL - 215 N2 - Human sperm motility is essential for fertilization and among pathologies underlying male infertility is asthenozoospermia. Nevertheless, mechanisms regulating sperm motility are not completely unraveled. This work investigates phosphoproteins underlying human sperm motility by using differential phosphoproteomic in two human sperm subpopulations: high (HM) and low (LM) motility, obtained by centrifugation in a density gradient. Phosphoproteomics (HPLC-MS/MS triple TOF), comparing human LM and HM phosphoproteomes, identified 210 phosphopeptides with different abundance that correspond with 119 sperm proteins. Analysis showed that 40% of phosphoproteins in LM spermatozoa are involved in metabolism, (catabolism, protein transport, lipid biosynthesis), 25% in spermatogenesis and sperm function, 8% in immune system and 6% in DNA repair. In HM spermatozoa, 48% of phosphoproteins are related to spermatogenesis and sperm function (motility), whereas 8% are associated to metabolism. GSK3α resulted one of the most abundant phosphoproteins in HM spermatozoa. Western blot confirmed that GSK3α phosphorylation is higher in HM spermatozoa. Summarizing, this study i) identified phosphoproteins in two human spermatozoa populations, ii) supports that human spermatozoa rely in protein phosphorylation, such as GSK3 α, to regulate sperm motility, iv) raises the challenge of using some identified human sperm phosphorylated proteins (GSK3α) as targets to develop into clinically relevant biomarkers. SIGNIFICANCE: Human sperm phosphoproteome analyzed by nano HPLC-MS/MS triple TOF identifies the differential abundance of sperm phosphoproteins in two human sperm populations exhibiting high motility (HM) and/or low motility (LM) that were isolated from normozoospermic healthy donors. Majority of human phosphoproteins found in LM spermatozoa are involved in sperm metabolism (40%), whereas those in HM spermatozoa are associated to spermatogenesis and sperm function, as motility (48%), and only 8% are associated to metabolism. One of the most abundant phosphoproteins found in HM spermatozoa is GSK3α, kinase directly involved in the regulation of sperm motility that was also validated by western blot. The biological relevance of this study is based in the fact that supports that mature human sperm cells rely in protein phosphorylation to efficiently regulate sperm motility and allows identifying those regulatory human sperm phosphoproteins. This work will clearly impacts the human reproductive field as it raises the challenge of consider identified human sperm phosphoproteins, such as GSK3α, as potential biological targets to develop into relevant biomarkers for the human clinic or assisted reproductive technology. SN - 1876-7737 UR - https://www.unboundmedicine.com/medline/citation/31972345/Human_sperm_phosphoproteome_reveals_differential_phosphoprotein_signatures_that_regulate_human_sperm_motility L2 - https://linkinghub.elsevier.com/retrieve/pii/S1874-3919(20)30022-1 DB - PRIME DP - Unbound Medicine ER -