{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T05:05:56Z","timestamp":1787375156952,"version":"build-2736575974"},"reference-count":41,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2015,8,25]],"date-time":"2015-08-25T00:00:00Z","timestamp":1440460800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Astaxanthin (Asta), a photo-protective red pigment of the carotenoid family, is known for its multiple beneficial properties. In this study, the effects of Asta on isolated human sperm were evaluated. Capacitation involves a series of transformations to let sperm acquire the correct features for potential oocyte fertilization, including the generation of a controlled amount of reactive oxygen species (ROS), cholesterol depletion of the sperm outer membrane, and protein tyrosine phosphorylation (Tyr-P) process in the head region. Volunteers, with normal spermiogram values, were divided in two separate groups on the basis of their ability to generate the correct content of endogenous ROS. Both patient group (PG) and control group (CG) were analysed for Tyr-phosphorylation (Tyr-P) pattern and percentages of acrosome-reacted cells (ARC) and non-viable cells (NVC), in the presence or absence of Asta. In addition, the involvement of ROS on membrane reorganization and the presence of Lyn, a Src family kinase associated with lipid rafts, were investigated. Results show that Lyn is present in the membranes of human sperm, mainly confined in midpiece in resting conditions. Following capacitation, Lyn translocated to the head concomitantly with raft relocation, thus allowing the Tyr-P of head proteins. Asta succeeded to trigger Lyn translocation in PG sperm thus bypassing the impaired ROS-related mechanism for rafts and Lyn translocation. In this study, we showed an interdependence between ROS generation and lipid rafts and Lyn relocation leading the cells to undergo the successive acrosome reaction (AR). Asta, by ameliorating PG sperm functioning, may be utilised to decrease male idiopathic infertility.<\/jats:p>","DOI":"10.3390\/md13095533","type":"journal-article","created":{"date-parts":[[2015,8,25]],"date-time":"2015-08-25T10:28:17Z","timestamp":1440498497000},"page":"5533-5551","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Astaxanthin Improves Human Sperm Capacitation by Inducing Lyn Displacement and Activation"],"prefix":"10.3390","volume":"13","author":[{"given":"Alessandra","family":"Andrisani","sequence":"first","affiliation":[{"name":"Department of Women\u2019s and Chilren\u2019s Health, University of Padova, Padova 35100, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Don\u00e0","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine-Biological Chemistry, University of Padova, Padova 35129, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Tibaldi","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine-Biological Chemistry, University of Padova, Padova 35129, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Brunati","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine-Biological Chemistry, University of Padova, Padova 35129, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Sabbadin","sequence":"additional","affiliation":[{"name":"Department of Medicine-Endocrinology, University of Padova, Padova 35100, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Decio","family":"Armanini","sequence":"additional","affiliation":[{"name":"Department of Medicine-Endocrinology, University of Padova, Padova 35100, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8177-3616","authenticated-orcid":false,"given":"Gualtiero","family":"Alvisi","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine-Microbiology Section, University of Padova, Padova 35129, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Gizzo","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Chilren\u2019s Health, University of Padova, Padova 35100, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Ambrosini","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Chilren\u2019s Health, University of Padova, Padova 35100, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0390-6823","authenticated-orcid":false,"given":"Eugenio","family":"Ragazzi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova 35129, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana","family":"Bordin","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine-Biological Chemistry, University of Padova, Padova 35129, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1016\/j.fertnstert.2013.01.111","article-title":"The use of genomics, proteomics, and metabolomics in identifying biomarkers of male infertility","volume":"99","author":"Kovac","year":"2013","journal-title":"Fertil. Steril."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1095\/biolreprod59.1.7","article-title":"Role of cholesterol in sperm capacitation","volume":"59","author":"Cross","year":"1998","journal-title":"Biol. Reprod."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/ncb0107-7","article-title":"Lipid rafts: At a crossroad between cell biology and physics","volume":"9","author":"Jacobson","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1093\/molehr\/gah154","article-title":"Various protein kinases regulate human sperm acrosome reaction and the associated phosphorylation of Tyr residues and of the Thr-Glu-Tyr motif","volume":"11","author":"Liguori","year":"2005","journal-title":"Mol. Hum. Reprod."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1242\/dev.121.4.1129","article-title":"Capacitation of mouse spermatozoa. I. Correlation between the capacitation state and protein tyrosine phosphorylation","volume":"121","author":"Visconti","year":"1995","journal-title":"Development"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1242\/jcs.111.5.645","article-title":"A novel signal transduction cascade in capacitating human spermatozoa characterised by a redox-regulated, cAMP-mediated induction of tyrosine phosphorylation","volume":"111","author":"Aitken","year":"1998","journal-title":"J. Cell Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/S0015-0282(99)00567-1","article-title":"Relationship between oxidative stress, semen characteristics, and clinical diagnosis in men undergoing infertility investigation","volume":"73","author":"Pasqualotto","year":"2000","journal-title":"Fertil. Steril."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/35036052","article-title":"Lipid rafts and signal transduction","volume":"1","author":"Simons","year":"2000","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1146\/annurev.biophys.32.110601.141803","article-title":"Model systems, lipid rafts, and cell membranes","volume":"33","author":"Simons","year":"2004","journal-title":"Annu. Rev. Biophys. Biomol. Struct."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/0005-2736(79)90260-8","article-title":"Studies on the mechanism of capacitation. II. Evidence for lipid transfer between plasma membrane of rat sperm and serum albumin during capacitation in vitro","volume":"558","author":"Davis","year":"1979","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1002\/jcp.21575","article-title":"Composition and significance of detergent resistant membranes in mouse spermatozoa","volume":"218","author":"Nixon","year":"2009","journal-title":"J. Cell. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1038\/sj.leu.2403446","article-title":"Transplantation studies in C3-deficient animals reveal a novel role of the third complement component (C3) in engraftment of bone marrow cells","volume":"18","author":"Ratajczak","year":"2004","journal-title":"Leukemia"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"239","DOI":"10.3109\/19396368.2014.904952","article-title":"Effect of various commercial buffers on sperm viability and capacitation","volume":"60","author":"Andrisani","year":"2014","journal-title":"Syst. Biol. Reprod. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2651","DOI":"10.1002\/jcp.22615","article-title":"Proteomic and functional analysis of human sperm detergent resistant membranes","volume":"226","author":"Nixon","year":"2011","journal-title":"J. Cell. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1095\/biolreprod.105.041533","article-title":"Isolation and proteomic analysis of mouse sperm detergent-resistant membrane fractions: Evidence for dissociation of lipid rafts during capacitation","volume":"73","author":"Sleight","year":"2005","journal-title":"Biol. Reprod."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1093\/humupd\/dmn004","article-title":"Oxidative stress and male infertility-a clinical perspective","volume":"14","author":"Tremellen","year":"2008","journal-title":"Hum. Reprod. Update."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2511","DOI":"10.1517\/14656566.2012.740011","article-title":"Male infertility: A critical review of pharmacologic management","volume":"13","author":"Hamada","year":"2012","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3264","DOI":"10.1093\/humrep\/der321","article-title":"Evaluation of correct endogenous reactive oxygen species content for human sperm capacitation and involvement of the NADPH oxidase system","volume":"26","author":"Fiore","year":"2011","journal-title":"Hum. Reprod."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1111\/j.1365-2605.2010.01097.x","article-title":"Endogenous reactive oxygen species content and modulation of tyrosine phosphorylation during sperm capacitation","volume":"34","author":"Fiore","year":"2011","journal-title":"Int. J. Androl."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.3390\/md11061909","article-title":"Effect of astaxanthin on human sperm capacitation","volume":"11","author":"Brunati","year":"2013","journal-title":"Mar. Drugs"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Lu, W., Fang, W., Li, J., Zhang, B., Yang, Q., Yan, X., Peng, L., Ai, H., Wang, J.J., and Liu, X. (2015). Phosphorylation of tyrosine Y1070 at the GluN2B subunit is regulated by synaptic activity and critical for surface expression of NMDA receptors. J. Biol. Chem.","DOI":"10.1074\/jbc.M115.663450"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1095\/biolreprod67.1.301","article-title":"Regulation of the human sperm tyrosine kinase c-yes. Activation by cyclic adenosine 3\u2032,5\u2032-monophosphate and inhibition by Ca(2+)","volume":"67","author":"Leclerc","year":"2002","journal-title":"Biol. Reprod."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1095\/biolreprod.108.070367","article-title":"Increased activity of the human sperm tyrosine kinase SRC by the cAMP-dependent pathway in the presence of calcium","volume":"79","author":"Lawson","year":"2008","journal-title":"Biol. Reprod."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2274","DOI":"10.1093\/humrep\/der232","article-title":"Light-mediated activation reveals a key role for protein kinase A and sarcoma protein kinase in the development of sperm hyper-activated motility","volume":"26","author":"Shahar","year":"2011","journal-title":"Hum. Reprod."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.ydbio.2003.09.032","article-title":"Requirement of protein tyrosine kinase and phosphatase activities for human sperm exocytosis","volume":"265","author":"Tomes","year":"2004","journal-title":"Dev. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1146\/annurev.cellbio.13.1.513","article-title":"Cellular functions regulated by Src family kinases","volume":"13","author":"Thomas","year":"1997","journal-title":"Annu. Rev. Cell. Dev. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1074\/jbc.271.2.695","article-title":"Discovery of a novel, potent, and Src family-selective tyrosine kinase inhibitor. Study of Lck- and FynT-dependent T cell activation","volume":"271","author":"Hanke","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.ucl.2008.01.003","article-title":"Endocrine manipulation in male infertility","volume":"35","author":"Kim","year":"2008","journal-title":"Urol. Clin. North Am."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1007\/s002530051061","article-title":"Antioxidant role of astaxanthin in the green alga Haematococcus pluvialis","volume":"48","author":"Kobayashi","year":"1997","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.jnutbio.2009.01.011","article-title":"Astaxanthin protects mitochondrial redox state and functional integrity against oxidative stress","volume":"21","author":"Wolf","year":"2010","journal-title":"J. Nutr. Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"58D","DOI":"10.1016\/j.amjcard.2008.02.010","article-title":"Astaxanthin: A novel potential treatment for oxidative stress and inflammation in cardiovascular disease","volume":"101","author":"Pashkow","year":"2008","journal-title":"Am. J. Cardiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2652","DOI":"10.1093\/humrep\/den314","article-title":"Src activation triggers capacitation and acrosome reaction but not motility in human spermatozoa","volume":"23","author":"Varano","year":"2008","journal-title":"Hum. Reprod."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/molehr\/gan007","article-title":"Investigation of the role of SRC in capacitation-associated tyrosine phosphorylation of human spermatozoa","volume":"14","author":"Mitchell","year":"2008","journal-title":"Mol. Hum. Reprod."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Lee, J.S., Kwon, W.S., Rahman, M.S., Yoon, S.J., Park, Y.J., and Pang, M.G. (2015). Actin-related protein 2\/3 complex-based actin polymerization is critical for male fertility. Andrology.","DOI":"10.1111\/andr.12076"},{"key":"ref_35","unstructured":"World Health Organization (2010). WHO Laboratory Manual for the Examination and Processing of Human Semen, Cambridge University Press."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1002\/j.1939-4640.2002.tb02324.x","article-title":"Oxidative stress and male infertility: From research bench to clinical practice","volume":"23","author":"Saleh","year":"2002","journal-title":"J. Androl."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1002\/jcp.1041510305","article-title":"Reactive oxygen species and human spermatozoa analysis of the cellular mechanisms involved in luminol- and lucigenin-dependent chemiluminescence","volume":"151","author":"Aitken","year":"1992","journal-title":"J. Cell. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2139","DOI":"10.1093\/humrep\/13.8.2139","article-title":"Effect of seminal plasma on capacitation and hyperactivation in human spermatozoa","volume":"13","author":"Mortimer","year":"1998","journal-title":"Hum. Reprod."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1111\/j.1439-0531.2004.00494.x","article-title":"Effect of exogenous progesterone on post-thaw capacitation and acrosome reaction of bovine sperm","volume":"39","author":"Lukoseviciute","year":"2004","journal-title":"Reprod. Domest. Anim."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1002\/jcb.21670","article-title":"Src-Tyrosine kinases are major agents in mitochondrial tyrosine phosphorylation","volume":"104","author":"Tibaldi","year":"2008","journal-title":"J. Cell. Biochem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4505","DOI":"10.1021\/pr500524p","article-title":"Diagnosis and prognosis of male infertility in mammal: The focusing of tyrosine phosphorylation and phosphotyrosine proteins","volume":"13","author":"Kwon","year":"2014","journal-title":"J. Proteome Res."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/13\/9\/5533\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:47:21Z","timestamp":1760215641000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/13\/9\/5533"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,8,25]]},"references-count":41,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2015,9]]}},"alternative-id":["md13095533"],"URL":"https:\/\/doi.org\/10.3390\/md13095533","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,8,25]]}}}