{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T03:42:01Z","timestamp":1790566921621,"version":"4.1.0"},"reference-count":152,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T00:00:00Z","timestamp":1695772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Regional Development Fund (ERDF)","award":["POCI-01-0145-FEDER-028599"],"award-info":[{"award-number":["POCI-01-0145-FEDER-028599"]}]},{"name":"European Regional Development Fund (ERDF)","award":["POCI-01-0145-FEDER-029311"],"award-info":[{"award-number":["POCI-01-0145-FEDER-029311"]}]},{"name":"European Regional Development Fund (ERDF)","award":["UIDB\/04539\/2020"],"award-info":[{"award-number":["UIDB\/04539\/2020"]}]},{"name":"European Regional Development Fund (ERDF)","award":["UIDP\/04539\/2020"],"award-info":[{"award-number":["UIDP\/04539\/2020"]}]},{"name":"European Regional Development Fund (ERDF)","award":["LA\/P\/0058\/2020"],"award-info":[{"award-number":["LA\/P\/0058\/2020"]}]},{"name":"European Regional Development Fund (ERDF)","award":["POCI-01-0145-FEDER-402-022125"],"award-info":[{"award-number":["POCI-01-0145-FEDER-402-022125"]}]},{"name":"European Regional Development Fund (ERDF)","award":["2021.05170.BD"],"award-info":[{"award-number":["2021.05170.BD"]}]},{"name":"European Regional Development Fund (ERDF)","award":["SFRH\/BD\/129429\/2017"],"award-info":[{"award-number":["SFRH\/BD\/129429\/2017"]}]},{"name":"National Mass Spectrometry Network (RNEM)","award":["POCI-01-0145-FEDER-028599"],"award-info":[{"award-number":["POCI-01-0145-FEDER-028599"]}]},{"name":"National Mass Spectrometry Network (RNEM)","award":["POCI-01-0145-FEDER-029311"],"award-info":[{"award-number":["POCI-01-0145-FEDER-029311"]}]},{"name":"National Mass Spectrometry Network (RNEM)","award":["UIDB\/04539\/2020"],"award-info":[{"award-number":["UIDB\/04539\/2020"]}]},{"name":"National Mass Spectrometry Network (RNEM)","award":["UIDP\/04539\/2020"],"award-info":[{"award-number":["UIDP\/04539\/2020"]}]},{"name":"National Mass Spectrometry Network (RNEM)","award":["LA\/P\/0058\/2020"],"award-info":[{"award-number":["LA\/P\/0058\/2020"]}]},{"name":"National Mass Spectrometry Network (RNEM)","award":["POCI-01-0145-FEDER-402-022125"],"award-info":[{"award-number":["POCI-01-0145-FEDER-402-022125"]}]},{"name":"National Mass Spectrometry Network (RNEM)","award":["2021.05170.BD"],"award-info":[{"award-number":["2021.05170.BD"]}]},{"name":"National Mass Spectrometry Network (RNEM)","award":["SFRH\/BD\/129429\/2017"],"award-info":[{"award-number":["SFRH\/BD\/129429\/2017"]}]},{"name":"FCT","award":["POCI-01-0145-FEDER-028599"],"award-info":[{"award-number":["POCI-01-0145-FEDER-028599"]}]},{"name":"FCT","award":["POCI-01-0145-FEDER-029311"],"award-info":[{"award-number":["POCI-01-0145-FEDER-029311"]}]},{"name":"FCT","award":["UIDB\/04539\/2020"],"award-info":[{"award-number":["UIDB\/04539\/2020"]}]},{"name":"FCT","award":["UIDP\/04539\/2020"],"award-info":[{"award-number":["UIDP\/04539\/2020"]}]},{"name":"FCT","award":["LA\/P\/0058\/2020"],"award-info":[{"award-number":["LA\/P\/0058\/2020"]}]},{"name":"FCT","award":["POCI-01-0145-FEDER-402-022125"],"award-info":[{"award-number":["POCI-01-0145-FEDER-402-022125"]}]},{"name":"FCT","award":["2021.05170.BD"],"award-info":[{"award-number":["2021.05170.BD"]}]},{"name":"FCT","award":["SFRH\/BD\/129429\/2017"],"award-info":[{"award-number":["SFRH\/BD\/129429\/2017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The global trend of rising (male) infertility is concerning, and the unidentifiable causes in half of the cases, the so-called unknown origin male infertility (UOMI), demands a better understanding and assessment of both external\/internal factors and mechanisms potentially involved. In this work, it was our aim to obtain new insight on UOMI, specifically on idiopathic (ID) and Unexplained male infertility (UMI), relying on a detailed evaluation of the male gamete, including functional, metabolic and proteomic aspects. For this purpose, 1114 semen samples, from males in couples seeking infertility treatment, were collected at the Reproductive Medicine Unit from the Centro Hospitalar e Universit\u00e1rio de Coimbra (CHUC), from July 2018\u2013July 2022. Based on the couples\u2019 clinical data, seminal\/hormonal analysis, and strict eligibility criteria, samples were categorized in 3 groups, control (CTRL), ID and UMI. Lifestyle factors and anxiety\/depression symptoms were assessed via survey. Sperm samples were evaluated functionally, mitochondrially and using proteomics. The results of Assisted Reproduction Techniques were assessed whenever available. According to our results, ID patients presented the worst sperm functional profile, while UMI patients were similar to controls. The proteomic analysis revealed 145 differentially expressed proteins, 8 of which were specifically altered in ID and UMI samples. Acrosin (ACRO) and sperm acrosome membrane-associated protein 4 (SACA4) were downregulated in ID patients while laminin subunit beta-2 (LAMB2), mannose 6-phosphate isomerase (MPI), ATP-dependent 6-phosphofructokinase liver type (PFKAL), STAR domain-containing protein 10 (STA10), serotransferrin (TRFE) and exportin-2 (XPO2) were downregulated in UMI patients. Using random forest analysis, SACA4 and LAMB2 were identified as the sperm proteins with a higher chance of distinguishing ID and UMI patients, and their function and expression variation were in accordance with the functional results. No alterations were observed in terms of lifestyle and psychological factors among the 3 groups. These findings obtained in an experimental setting based on 3 well-defined groups of subjects, might help to validate new biomarkers for unknown origin male infertility (ID and UMI) that, in the future, can be used to improve diagnostics and treatments.<\/jats:p>","DOI":"10.3390\/biom13101462","type":"journal-article","created":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T01:42:12Z","timestamp":1695865332000},"page":"1462","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["New Insights on Sperm Function in Male Infertility of Unknown Origin: A Multimodal Approach"],"prefix":"10.3390","volume":"13","author":[{"given":"Rita I.","family":"Pacheco","sequence":"first","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria I.","family":"Cristo","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"IIIUC\u2014Institute for Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2180-3518","authenticated-orcid":false,"given":"Sandra I.","family":"Anjo","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"IIIUC\u2014Institute for Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8157-0819","authenticated-orcid":false,"given":"Andreia F.","family":"Silva","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"IIIUC\u2014Institute for Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria In\u00eas","family":"Sousa","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, 3000-456 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata S.","family":"Tavares","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, 3000-456 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Paula","family":"Sousa","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Reproductive Medicine Unit, Centro Hospitalar e Universit\u00e1rio de Coimbra, 3000-075 Coimbra, Portugal"},{"name":"Eugin Coimbra, Rua Filipe Hodart 12, 3000-185 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7423-2996","authenticated-orcid":false,"given":"Teresa","family":"Almeida Santos","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Reproductive Medicine Unit, Centro Hospitalar e Universit\u00e1rio de Coimbra, 3000-075 Coimbra, Portugal"},{"name":"Eugin Coimbra, Rua Filipe Hodart 12, 3000-185 Coimbra, Portugal"},{"name":"Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7542-0497","authenticated-orcid":false,"given":"Mariana","family":"Moura-Ramos","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Unit, Centro Hospitalar e Universit\u00e1rio de Coimbra, 3000-075 Coimbra, Portugal"},{"name":"Eugin Coimbra, Rua Filipe Hodart 12, 3000-185 Coimbra, Portugal"},{"name":"Center for Research in Neuropsychology and Cognitive and Behavioral Intervention, Faculty of Psychology and Educational Sciences, University of Coimbra, 3000-115 Coimbra, Portugal"},{"name":"Clinical Psychology Unit, Centro Hospitalar e Universit\u00e1rio de Coimbra, 3000-075 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0015-8604","authenticated-orcid":false,"given":"Francisco","family":"Caramelo","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2087-4042","authenticated-orcid":false,"given":"Bruno","family":"Manadas","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"IIIUC\u2014Institute for Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1172-4018","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Ramalho-Santos","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, 3000-456 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra Gomes","family":"Amaral","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"IIIUC\u2014Institute for Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,27]]},"reference":[{"key":"ref_1","unstructured":"Salonia, A., Bettocchi, C., Capogrosso, P., Carvalho, J., Corona, G., Hatzichristodoulou, G., Jones, T.H., Kadioglu, A., Martinez-Salamanca, J.I., and Minhas, S. (2023, January 10\u201313). EAU Guidelines. Proceedings of the EAU Annual Congress, Milan, Italy."},{"key":"ref_2","first-page":"102","article-title":"The economic impact of infertility on women in developing countries\u2014A systematic review","volume":"4","author":"Dyer","year":"2012","journal-title":"Facts Views Vis. Obgyn."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.fertnstert.2020.09.155","article-title":"Fertility-a human right worthy of mandated insurance coverage: The evolution, limitations, and future of access to care","volume":"115","author":"Kawwass","year":"2021","journal-title":"Fertil. Steril."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"203","DOI":"10.3109\/14647273.2014.942390","article-title":"The psychological impact of infertility and fertility treatment on the male partner","volume":"17","author":"Dooley","year":"2014","journal-title":"Hum. Fertil."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Agarwal, A., Mulgund, A., Hamada, A., and Chyatte, M.R. (2015). A unique view on male infertility around the globe. Reprod. Biol. Endocrinol., 13.","DOI":"10.1186\/s12958-015-0032-1"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s00345-011-0726-8","article-title":"Influence of urogenital infections and inflammation on semen quality and male fertility","volume":"30","author":"Rusz","year":"2012","journal-title":"World J. Urol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1210\/er.2009-0002","article-title":"Endocrine-disrupting chemicals: An Endocrine Society scientific statement","volume":"30","author":"Bourguignon","year":"2009","journal-title":"Endocr. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.eururo.2021.08.014","article-title":"European Association of Urology Guidelines on Male Sexual and Reproductive Health: 2021 Update on Male Infertility","volume":"80","author":"Minhas","year":"2021","journal-title":"Eur. Urol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1046\/j.1365-2605.2000.00250.x","article-title":"The advantages of standardized evaluation of male infertility","volume":"23","author":"Pierik","year":"2000","journal-title":"Int. J. Androl."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1097\/01.XHA.0000397686.82729.09","article-title":"Unexplained male infertility: Potential causes and management","volume":"1","author":"Hamada","year":"2011","journal-title":"Hum. Androl."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Arafa, M., Agarwal, A., Majzoub, A., Panner Selvam, M.K., Baskaran, S., Henkel, R., and Elbardisi, H. (2020). Efficacy of antioxidant supplementation on conventional and advanced sperm function tests in patients with idiopathic male infertility. Antioxidants, 9.","DOI":"10.3390\/antiox9030219"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1590\/S1677-55382012000500002","article-title":"Unexplained male infertility: Diagnosis and management","volume":"38","author":"Hamada","year":"2012","journal-title":"Int. Braz. J. Urol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/0020-7292(92)90257-J","article-title":"Unexplained infertility: A review of diagnosis, prognosis, treatment efficacy and management","volume":"39","author":"Collins","year":"1992","journal-title":"Int. J. Gynaecol. Obs."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"27","DOI":"10.2174\/1874255601103010027","article-title":"The role of contemporary andrology in unraveling the mystery of unexplained male infertility","volume":"3","author":"Hamada","year":"2011","journal-title":"Open Reprod. Sci. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1093\/humupd\/dmt046","article-title":"The combined human sperm proteome: Cellular pathways and implications for basic and clinical science","volume":"20","author":"Amaral","year":"2014","journal-title":"Hum. Reprod. Update"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Moscatelli, N., Lunetti, P., Braccia, C., Armirotti, A., Pisanello, F., De Vittorio, M., Zara, V., and Ferramosca, A. (2019). Comparative proteomic analysis of proteins involved in bioenergetics pathways associated with human sperm motility. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20123000"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1007\/s00345-013-1023-5","article-title":"Comparative proteomic study between human normal motility sperm and idiopathic asthenozoospermia","volume":"31","author":"Shen","year":"2013","journal-title":"World J. Urol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5426","DOI":"10.1016\/j.jprot.2012.06.021","article-title":"Proteomic characteristics of spermatozoa in normozoospermic patients with infertility","volume":"75","author":"Xu","year":"2012","journal-title":"J. Proteom."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Panner Selvam, M.K., Agarwal, A., Pushparaj, P.N., Baskaran, S., and Bendou, H. (2019). Sperm proteome analysis and identification of fertility-associated biomarkers in unexplained male infertility. Genes, 10.","DOI":"10.3390\/genes10070522"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"544","DOI":"10.4103\/aja.aja_121_18","article-title":"Proteomic analysis of seminal plasma from bilateral varicocele patients indicates an oxidative state and increased inflammatory response","volume":"21","author":"Agarwal","year":"2019","journal-title":"Asian J. Androl."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.eursup.2014.08.002","article-title":"Diagnosis of male infertility: Diagnostic work-up of the infertile man","volume":"13","author":"Kliesch","year":"2014","journal-title":"Eur. Urol. Suppl."},{"key":"ref_22","unstructured":"WHO Organization (2010). WHO Laboratory Manual for the Examination and Processing of Human Semen, WHO."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1530\/REP-15-0100","article-title":"High glucose concentrations per se do not adversely affect human sperm function in vitro","volume":"150","author":"Portela","year":"2015","journal-title":"Reproduction"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1111\/j.1600-0447.1983.tb09716.x","article-title":"The hospital anxiety and depression scale","volume":"67","author":"Zigmond","year":"1983","journal-title":"Acta Psychiatr Scand."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1080\/13548500500524088","article-title":"Validation study of a Portuguese version of the Hospital Anxiety and Depression Scale","volume":"12","author":"Silva","year":"2007","journal-title":"Psychol. Health Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1111\/famp.12364","article-title":"The Role of Dyadic Coping on the Marital and Emotional Adjustment of Couples With Infertility","volume":"58","author":"Chaves","year":"2019","journal-title":"Fam. Process"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1186\/s12955-017-0759-9","article-title":"Is the Hospital Anxiety and Depression Scale (HADS) a valid measure in a general population 65\u201380 years old? A psychometric evaluation study","volume":"15","author":"Djukanovic","year":"2017","journal-title":"Health Qual. Life Outcomes"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1093\/humrep\/den365","article-title":"Dual use of Diff-Quik-like stains for the simultaneous evaluation of human sperm morphology and chromatin status","volume":"24","author":"Sousa","year":"2009","journal-title":"Hum. Reprod."},{"key":"ref_29","first-page":"394","article-title":"Probing the structure and function of mammalian sperm using optical and fluorescence microscopy","volume":"1","author":"Amaral","year":"2007","journal-title":"Mod. Res. Educ. Top. Microsc."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1111\/j.2047-2927.2013.00098.x","article-title":"UVB irradiation as a tool to assess ROS-induced damage in human spermatozoa","volume":"1","author":"Amaral","year":"2013","journal-title":"Andrology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"72","DOI":"10.3109\/19396368.2013.867380","article-title":"Concentration-dependent Sildenafil citrate (Viagra) effects on ROS production, energy status, and human sperm function","volume":"60","author":"Sousa","year":"2014","journal-title":"Syst. Biol. Reprod. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1111\/j.2047-2927.2013.00127.x","article-title":"Evaluation of human sperm chromatin status after selection using a modified Diff-Quik stain indicates embryo quality and pregnancy outcomes following in vitro fertilization","volume":"1","author":"Tavares","year":"2013","journal-title":"Andrology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1002\/pmic.201400221","article-title":"Short GeLC-SWATH: A fast and reliable quantitative approach for proteomic screenings","volume":"15","author":"Anjo","year":"2015","journal-title":"Proteomics"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1038\/nmeth.2703","article-title":"Quantifying protein interaction dynamics by SWATH mass spectrometry: Application to the 14-3-3 system","volume":"10","author":"Collins","year":"2013","journal-title":"Nat. Methods"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Gillet, L.C., Navarro, P., Tate, S., R\u00f6st, H., Selevsek, N., Reiter, L., Bonner, R., and Aebersold, R. (2012). Targeted data extraction of the MS\/MS spectra generated by data-independent acquisition: A new concept for consistent and accurate proteome analysis. Mol. Cell. Proteom., 11.","DOI":"10.1074\/mcp.O111.016717"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Sennels, L., Bukowski-Wills, J.-C., and Rappsilber, J. (2009). Improved results in proteomics by use of local and peptide-class specific false discovery rates. BMC Bioinform., 10.","DOI":"10.1186\/1471-2105-10-179"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3661","DOI":"10.1021\/pr070492f","article-title":"Nonlinear fitting method for determining local false discovery rates from decoy database searches","volume":"7","author":"Tang","year":"2008","journal-title":"J. Proteome Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1038\/nmeth.2702","article-title":"Mapping differential interactomes by affinity purification coupled with data-independent mass spectrometry acquisition","volume":"10","author":"Lambert","year":"2013","journal-title":"Nat. Methods"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"120163","DOI":"10.1016\/j.talanta.2019.120163","article-title":"Use of recombinant proteins as a simple and robust normalization method for untargeted proteomics screening: Exhaustive performance assessment","volume":"205","author":"Anjo","year":"2019","journal-title":"Talanta"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"D543","DOI":"10.1093\/nar\/gkab1038","article-title":"The PRIDE database resources in 2022: A hub for mass spectrometry-based proteomics evidences","volume":"50","author":"Bai","year":"2022","journal-title":"Nucleic Acids Res"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/s41596-019-0128-8","article-title":"Protocol Update for large-scale genome and gene function analysis with the PANTHER classification system (v.14.0)","volume":"14","author":"Mi","year":"2019","journal-title":"Nat. Protoc."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources","volume":"4","author":"Huang","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2597","DOI":"10.1002\/pmic.201400515","article-title":"FunRich: An open access standalone functional enrichment and interaction network analysis tool","volume":"15","author":"Pathan","year":"2015","journal-title":"Proteomics"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Chong, J., Wishart, D.S., and Xia, J. (2019). Using MetaboAnalyst 4.0 for Comprehensive and Integrative Metabolomics Data Analysis. Curr. Protoc. Bioinform., 68.","DOI":"10.1002\/cpbi.86"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1095\/biolreprod13.1.83","article-title":"Proacrosin from rabbit epididymal spermatozoa: Partial purification and initial biochemical characterization","volume":"13","author":"Meizel","year":"1975","journal-title":"Biol. Reprod."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2513","DOI":"10.1073\/pnas.1917595117","article-title":"Acrosin is essential for sperm penetration through the zona pellucida in hamsters","volume":"117","author":"Hirose","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1002\/jez.1402360214","article-title":"Proteolysis of the zona pellucida by acrosin: The nature of the hydrolysis products","volume":"236","author":"Urch","year":"1985","journal-title":"J. Exp. Zool."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"31845","DOI":"10.1016\/S0021-9258(18)31772-1","article-title":"Sperm from mice carrying a targeted mutation of the acrosin gene can penetrate the oocyte zona pellucida and effect fertilization","volume":"269","author":"Baba","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_49","first-page":"229","article-title":"Determination of sperm acrosin activity for evaluation of male fertility","volume":"2","author":"Cui","year":"2000","journal-title":"Asian J. Androl."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1093\/humrep\/dey335","article-title":"Mitochondrial functionality modifies human sperm acrosin activity, acrosome reaction capability and chromatin integrity","volume":"34","author":"Zhang","year":"2019","journal-title":"Hum. Reprod."},{"key":"ref_51","first-page":"129","article-title":"In vitro effect of cell phone radiation on motility, DNA fragmentation and clusterin gene expression in human sperm","volume":"9","author":"Zalata","year":"2015","journal-title":"Int. J. Fertil. Steril."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"103478","DOI":"10.1016\/j.jprot.2019.103478","article-title":"Proteomics analysis of asthenozoospermia and identification of glucose-6-phosphate isomerase as an important enzyme for sperm motility","volume":"208","author":"Guo","year":"2019","journal-title":"J. Proteom."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/S0015-0282(16)46044-9","article-title":"A study of sperm acrosin in patients with unexplained infertility","volume":"37","author":"Mohsenian","year":"1982","journal-title":"Fertil. Steril."},{"key":"ref_54","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_55","doi-asserted-by":"crossref","first-page":"30506","DOI":"10.1074\/jbc.M301713200","article-title":"SAMP14, a novel, acrosomal membrane-associated, glycosylphosphatidylinositol-anchored member of the Ly-6\/urokinase-type plasminogen activator receptor superfamily with a role in sperm-egg interaction","volume":"278","author":"Shetty","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1095\/biolreprod.111.092254","article-title":"The laminin-induced acrosome reaction in human sperm is mediated by Src kinases and the proteasome","volume":"85","author":"Tapia","year":"2011","journal-title":"Biol. Reprod."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1093\/glycob\/cwf060","article-title":"Molecular cloning, gene organization, and expression of mouse Mpi encoding phosphomannose isomerase","volume":"12","author":"Davis","year":"2002","journal-title":"Glycobiology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"5916","DOI":"10.1074\/jbc.M511982200","article-title":"Ablation of mouse phosphomannose isomerase (Mpi) causes mannose 6-phosphate accumulation, toxicity, and embryonic lethality","volume":"281","author":"DeRossi","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"103654","DOI":"10.1016\/j.jprot.2020.103654","article-title":"Human sperm phosphoproteome reveals differential phosphoprotein signatures that regulate human sperm motility","volume":"215","author":"Serrano","year":"2020","journal-title":"J. Proteom."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1126\/science.1222278","article-title":"PFK1 glycosylation is a key regulator of cancer cell growth and central metabolic pathways","volume":"337","author":"Yi","year":"2012","journal-title":"Science"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Park, Y.-J., and Pang, M.-G. (2021). Mitochondrial functionality in male fertility: From spermatogenesis to fertilization. Antioxidants, 10.","DOI":"10.3390\/antiox10010098"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1530\/eje.0.1380322","article-title":"Changes in carbohydrate metabolism of testicular germ cells during meiosis in the rat","volume":"138","author":"Bajpai","year":"1998","journal-title":"Eur. J. Endocrinol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1002\/prca.201200078","article-title":"Differential proteomic profiling in human spermatozoa that did or did not result in pregnancy via IVF and AID","volume":"7","author":"Zhu","year":"2013","journal-title":"Proteom.\u2013Clin. Appl."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3538","DOI":"10.1158\/0008-5472.CAN-03-3731","article-title":"The phosphoprotein StarD10 is overexpressed in breast cancer and cooperates with ErbB receptors in cellular transformation","volume":"64","author":"Olayioye","year":"2004","journal-title":"Cancer Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"27436","DOI":"10.1074\/jbc.M413330200","article-title":"StarD10, a START domain protein overexpressed in breast cancer, functions as a phospholipid transfer protein","volume":"280","author":"Olayioye","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s43032-020-00260-0","article-title":"Semen Biochemical Components in Varicocele, Leukocytospermia, and Idiopathic Infertility","volume":"28","author":"Collodel","year":"2021","journal-title":"Reprod. Sci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.theriogenology.2014.05.024","article-title":"Seminal plasma proteins of adult boars and correlations with sperm parameters","volume":"82","author":"Martins","year":"2014","journal-title":"Theriogenology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"9523","DOI":"10.1016\/S0021-9258(18)43419-9","article-title":"Sertoli cells synthesize and secrete transferrin-like protein","volume":"255","author":"Skinner","year":"1980","journal-title":"J. Biol. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1095\/biolreprod27.1.211","article-title":"Secretion of testicular transferrin by cultured Sertoli cells is regulated by hormones and retinoids","volume":"27","author":"Skinner","year":"1982","journal-title":"Biol. Reprod."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.3892\/ijo.2016.3388","article-title":"Cellular apoptosis susceptibility (CAS) is overexpressed in thyroid carcinoma and maintains tumor cell growth: A potential link to the BRAFV600E mutation","volume":"48","author":"Holzer","year":"2016","journal-title":"Int. J. Oncol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"13077","DOI":"10.1007\/s13277-016-5301-x","article-title":"CAS (CSE1L) signaling pathway in tumor progression and its potential as a biomarker and target for targeted therapy","volume":"37","author":"Jiang","year":"2016","journal-title":"Tumour Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e12549","DOI":"10.1111\/cpr.12549","article-title":"CSE1L participates in regulating cell mitosis in human seminoma","volume":"52","author":"Liu","year":"2019","journal-title":"Cell Prolif."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2627","DOI":"10.1016\/j.yexcr.2013.07.030","article-title":"AKT activation drives the nuclear localization of CSE1L and a pro-oncogenic transcriptional activation in ovarian cancer cells","volume":"319","author":"Lorenzato","year":"2013","journal-title":"Exp. Cell Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2446","DOI":"10.1096\/fj.11-195982","article-title":"The cellular apoptosis susceptibility CAS\/CSE1L gene protects ovarian cancer cells from death by suppressing RASSF1C","volume":"26","author":"Lorenzato","year":"2012","journal-title":"FASEB J."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"5670","DOI":"10.1021\/pr500652y","article-title":"Identification of proteins involved in human sperm motility using high-throughput differential proteomics","volume":"13","author":"Amaral","year":"2014","journal-title":"J. Proteome Res."},{"key":"ref_76","first-page":"90","article-title":"Unexplained male infertility\u2014Looking beyond routine semen analysis","volume":"7","author":"Hamada","year":"2012","journal-title":"Eur. Urol. Rev."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1016\/j.fertnstert.2014.10.021","article-title":"Limitations of semen analysis as a test of male fertility and anticipated needs from newer tests","volume":"102","author":"Wang","year":"2014","journal-title":"Fertil. Steril."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.urology.2014.04.043","article-title":"Functional sperm testing and the role of proteomics in the evaluation of male infertility","volume":"84","author":"Barazani","year":"2014","journal-title":"Urology"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Schattman, G.L., Esteves, S.C., and Agarwal, A. (2015). Unexplained Infertility: Pathophysiology, Evaluation and Treatment, Springer.","DOI":"10.1007\/978-1-4939-2140-9"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1590\/S1807-59322011000400026","article-title":"An update on the clinical assessment of the infertile male","volume":"66","author":"Esteves","year":"2011","journal-title":"Clinics"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"164","DOI":"10.4081\/aiua.2014.3.164","article-title":"Is there a place for nutritional supplements in the treatment of idiopathic male infertility?","volume":"86","author":"Arcaniolo","year":"2014","journal-title":"Arch. Ital. Urol. Androl."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e13158","DOI":"10.1111\/and.13158","article-title":"Difference in the seminal plasma protein expression in unexplained infertile men with successful and unsuccessful in vitro fertilisation outcome","volume":"51","author":"Kanannejad","year":"2019","journal-title":"Andrologia"},{"key":"ref_83","first-page":"354","article-title":"Is There a Relevant Clinical Impact in Differentiating Idiopathic versus Unexplained Male Infertility?","volume":"40","author":"Corsini","year":"2021","journal-title":"World J. Men\u2019s Health"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.eururo.2016.06.044","article-title":"Varicocele is associated with impaired semen quality and reproductive hormone levels: A study of 7035 healthy young men from six European countries","volume":"70","author":"Damsgaard","year":"2016","journal-title":"Eur. Urol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1016\/j.fertnstert.2020.04.045","article-title":"Differential DNA methylation pattern and sperm quality in men with varicocele","volume":"114","author":"Santana","year":"2020","journal-title":"Fertil. Steril."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"4336","DOI":"10.1038\/s41598-019-40707-2","article-title":"Reduced sperm telomere length in individuals with varicocele is associated with reduced genomic integrity","volume":"9","author":"Tahamtan","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2","DOI":"10.26444\/aaem\/106085","article-title":"Effect of ionizing radiation on the male reproductive system","volume":"26","author":"Wdowiak","year":"2019","journal-title":"Ann. Agric. Environ. Med."},{"key":"ref_88","first-page":"160","article-title":"Fertility and occupational hazards: Review of the literature","volume":"13","author":"Ashiru","year":"2009","journal-title":"Afr. J. Reprod. Health"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1179\/oeh.2006.12.4.355","article-title":"Semen quality and reproductive sex hormone levels in Peruvian pesticide sprayers","volume":"12","author":"Yucra","year":"2006","journal-title":"Int. J. Occup. Environ. Health"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1136\/oem.49.1.5","article-title":"Semen quality in welders exposed to radiant heat","volume":"49","author":"Bonde","year":"1992","journal-title":"Occup. Environ. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"101","DOI":"10.2174\/1745017901915010101","article-title":"Depression and anxiety in pathways of medically assisted reproduction: The role of infertility stress dimensions","volume":"15","author":"Pozza","year":"2019","journal-title":"Clin. Pract. Epidemiol. Ment. Health CP EMH"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1016\/S0015-0282(03)00374-1","article-title":"Psychosocial factors discriminate oligozoospermic from normozoospermic men","volume":"79","author":"Balistreri","year":"2003","journal-title":"Fertil. Steril."},{"key":"ref_93","first-page":"172","article-title":"Oxidative Stress and Sperm Mitochondrial Dna Mutation in Idiopathic Oligoasthenozoospermic Men","volume":"46","author":"Kumar","year":"2009","journal-title":"Indian J. Biochem. Biophys."},{"key":"ref_94","first-page":"221","article-title":"Evaluation of sperm functional parameters in normozoospermic infertile individuals","volume":"37","author":"Cadavid","year":"2013","journal-title":"Actas Urol. Esp."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"12659","DOI":"10.1111\/and.12659","article-title":"Are oxidative stress markers associated with unexplained male infertility?","volume":"49","author":"Camargo","year":"2017","journal-title":"Andrologia"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1530\/REP-07-0152","article-title":"Is sperm evaluation useful in predicting human fertility?","volume":"134","author":"Lewis","year":"2007","journal-title":"Reproduction"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1093\/humupd\/dmg027","article-title":"Role of sperm chromatin abnormalities and DNA damage in male infertility","volume":"9","author":"Agarwal","year":"2003","journal-title":"Hum. Reprod. Update"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.abb.2009.02.003","article-title":"Signal transduction pathways that regulate sperm capacitation and the acrosome reaction","volume":"485","author":"Tulsiani","year":"2009","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_99","first-page":"289","article-title":"Biological basis for human capacitation\u2014Revisited","volume":"23","year":"2017","journal-title":"Hum. Reprod. Update"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"165","DOI":"10.2174\/1874609810902030165","article-title":"Aging, mitochondria and male reproductive function","volume":"2","author":"Amaral","year":"2009","journal-title":"Curr. Aging Sci."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Sousa, A.P., Amaral, A., Baptista, M., Tavares, R., Caballero Campo, P., Caballero Peregr\u00edn, P., Freitas, A., Paiva, A., Almeida-Santos, T., and Ramalho-Santos, J. (2011). Not all sperm are equal: Functional mitochondria characterize a subpopulation of human sperm with better fertilization potential. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0018112"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1111\/j.1439-0272.2010.01117.x","article-title":"Influence of mitochondrial membrane potential of spermatozoa on in vitro fertilisation outcome","volume":"44","author":"Marchetti","year":"2012","journal-title":"Andrologia"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"R163","DOI":"10.1530\/REP-13-0178","article-title":"Mitochondria functionality and sperm quality","volume":"146","author":"Amaral","year":"2013","journal-title":"Reproduction"},{"key":"ref_104","first-page":"32","article-title":"Correlation of sperm nuclear chromatin condensation staining method with semen parameters and sperm functional tests in patients with spinal cord injury, varicocele, and idiopathic infertility","volume":"3","author":"Salsabili","year":"2006","journal-title":"Urol. J."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Wu, W., Shen, O., Qin, Y., Niu, X., Lu, C., Xia, Y., Song, L., Wang, S., and Wang, X. (2010). Idiopathic male infertility is strongly associated with aberrant promoter methylation of methylenetetrahydrofolate reductase (MTHFR). PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0013884"},{"key":"ref_106","first-page":"747","article-title":"Effects of highly purified follicle-stimulating hormone on sperm DNA damage in men with male idiopathic subfertility: A pilot study","volume":"34","author":"Palomba","year":"2011","journal-title":"J. Endocrinol. Investig."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2676","DOI":"10.1016\/j.fertnstert.2011.05.026","article-title":"Activation of the immune system and sperm DNA fragmentation are associated with idiopathic oligoasthenoteratospermia in men with couple subfertility","volume":"95","author":"Pelliccione","year":"2011","journal-title":"Fertil. Steril."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/S0015-0282(02)03219-3","article-title":"Increased sperm nuclear DNA damage in normozoospermic infertile men: A prospective study","volume":"78","author":"Saleh","year":"2002","journal-title":"Fertil. Steril."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1093\/humrep\/dev053","article-title":"Aberrant DNA methylation patterns of spermatozoa in men with unexplained infertility","volume":"30","author":"Urdinguio","year":"2015","journal-title":"Hum. Reprod."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"101","DOI":"10.5653\/cerm.2015.42.3.101","article-title":"Sperm chromatin structure assay results in Nigerian men with unexplained infertility","volume":"42","author":"Faduola","year":"2015","journal-title":"Clin. Exp. Reprod. Med."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1111\/j.1439-0272.1997.tb00318.x","article-title":"Assessment of hyperactivation, acrosome reaction and motility characteristics of spermatozoa from semen of men of proven fertility and unexplained infertility","volume":"29","author":"Peedicayil","year":"1997","journal-title":"Andrologia"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1590\/S1677-55382007000500002","article-title":"Clinical relevance of oxidative stress and sperm chromatin damage in male infertility: An evidence based analysis","volume":"33","author":"Cocuzza","year":"2007","journal-title":"Int. Braz. J. Urol."},{"key":"ref_113","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_114","first-page":"184","article-title":"Free radicals and male reproduction","volume":"109","author":"Agarwal","year":"2011","journal-title":"J. Indian Med. Assoc."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.ab.2017.07.009","article-title":"Mitochondrial membrane potential","volume":"552","author":"Zorova","year":"2018","journal-title":"Anal. Biochem."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1002\/j.1939-4640.2001.tb02185.x","article-title":"Oxidative stress in normospermic men undergoing infertility evaluation","volume":"22","author":"Pasqualotto","year":"2001","journal-title":"J. Androl."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1111\/j.1745-7262.2007.00237.x","article-title":"Increased oxidative damage of sperm and seminal plasma in men with idiopathic infertility is higher in patients with glutathione S-transferase Mu-1 null genotype","volume":"9","author":"Aydemir","year":"2007","journal-title":"Asian J. Androl."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1016\/j.fertnstert.2012.11.045","article-title":"Mystery of idiopathic male infertility: Is oxidative stress an actual risk?","volume":"99","author":"Aktan","year":"2013","journal-title":"Fertil. Steril."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1080\/13880209.2017.1421672","article-title":"Protective effect of MOTILIPERM in varicocele-induced oxidative injury in rat testis by activating phosphorylated inositol requiring kinase 1\u03b1 (p-IRE1\u03b1) and phosphorylated c-Jun N-terminal kinase (p-JNK) pathways","volume":"56","author":"Soni","year":"2018","journal-title":"Pharm. Biol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1074\/mcp.M112.020552","article-title":"Human sperm tail proteome suggests new endogenous metabolic pathways","volume":"12","author":"Amaral","year":"2013","journal-title":"Mol. Cell. Proteom."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Petit, F.G., Kervarrec, C., Jamin, S.P., Smagulova, F., Hao, C., Becker, E., J\u00e9gou, B., Chalmel, F., and Primig, M. (2015). Combining RNA and protein profiling data with network interactions identifies genes associated with spermatogenesis in mouse and human. Biol. Reprod., 92.","DOI":"10.1095\/biolreprod.114.126250"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"2714","DOI":"10.1002\/pmic.201000799","article-title":"Proteomic characterization of the human sperm nucleus","volume":"11","author":"Castillo","year":"2011","journal-title":"Proteomics"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1002\/jcp.21623","article-title":"Biochemical characterization of membrane fractions in murine sperm: Identification of three distinct sub-types of membrane rafts","volume":"218","author":"Asano","year":"2009","journal-title":"J. Cell Physiol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s10719-020-09924-0","article-title":"Identification of lipid raft glycoproteins obtained from boar spermatozoa","volume":"37","author":"Fierro","year":"2020","journal-title":"Glycoconj. J."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Chen, L., Wen, C.W., Deng, M.J., Li, P., Zhang, Z.D., Zhou, Z.H., and Wang, X. (2020). Metabolic and transcriptional changes in seminal plasma of asthenozoospermia patients. Biomed. Chromatogr., 34.","DOI":"10.1002\/bmc.4769"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1007\/s10815-015-0474-6","article-title":"Mutation analysis in patients with total sperm immotility","volume":"32","author":"Pereira","year":"2015","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1016\/j.cell.2019.03.047","article-title":"Dual Sensing of Physiologic pH and Calcium by EFCAB9 Regulates Sperm Motility","volume":"177","author":"Hwang","year":"2019","journal-title":"Cell"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1095\/biolreprod.103.016675","article-title":"Equatorial segment protein defines a discrete acrosomal subcompartment persisting throughout acrosomal biogenesis","volume":"69","author":"Wolkowicz","year":"2003","journal-title":"Biol. Reprod."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"272","DOI":"10.2164\/jandrol.106.000604","article-title":"Equatorial segment protein (ESP) is a human alloantigen involved in sperm-egg binding and fusion","volume":"29","author":"Wolkowicz","year":"2008","journal-title":"J. Androl."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1016\/j.theriogenology.2010.04.025","article-title":"Biomarkers of in vivo fertility in sperm and seminal plasma of fertile stallions","volume":"74","author":"Novak","year":"2010","journal-title":"Theriogenology"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Xue, D., Zhang, Y., Wang, Y., Wang, J., An, F., Sun, X., and Yu, Z. (2019). Quantitative proteomic analysis of sperm in unexplained recurrent pregnancy loss. Reprod. Biol. Endocrinol., 17.","DOI":"10.1186\/s12958-019-0496-5"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1111\/andr.13215","article-title":"Expression of membrane fusion proteins in spermatozoa and total fertilisation failure during in vitro fertilisation","volume":"10","author":"Enoiu","year":"2022","journal-title":"Andrology"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"683920","DOI":"10.1155\/2013\/683920","article-title":"Neuroprotective function of DJ-1 in Parkinson\u2019s disease","volume":"2013","author":"Ariga","year":"2013","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"68","DOI":"10.3389\/fnmol.2018.00068","article-title":"Distinct Mechanisms of Pathogenic DJ-1 Mutations in Mitochondrial Quality Control","volume":"11","author":"Strobbe","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Wu, Y.Q., Rao, M., Hu, S.F., Ke, D.D., Zhu, C.H., and Xia, W. (2020). Effect of transient scrotal hyperthermia on human sperm: An iTRAQ-based proteomic analysis. Reprod. Biol. Endocrinol., 18.","DOI":"10.1186\/s12958-020-00640-w"},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Agarwal, A., Panner Selvam, M.K., Samanta, L., Vij, S.C., Parekh, N., Sabanegh, E., Tadros, N.N., Arafa, M., and Sharma, R. (2019). Effect of Antioxidant Supplementation on the Sperm Proteome of Idiopathic Infertile Men. Antioxidants, 8.","DOI":"10.3390\/antiox8100488"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"8826","DOI":"10.1073\/pnas.1401837111","article-title":"Skp1-Cullin-F-box (SCF)-type ubiquitin ligase FBXW7 negatively regulates spermatogonial stem cell self-renewal","volume":"111","author":"Onoyama","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"2637","DOI":"10.1101\/gad.287045.116","article-title":"Myc\/Mycn-mediated glycolysis enhances mouse spermatogonial stem cell self-renewal","volume":"30","author":"Tanaka","year":"2016","journal-title":"Genes. Dev."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"224","DOI":"10.3389\/fendo.2019.00224","article-title":"Molecular Mechanisms and Signaling Pathways Involved in Sertoli Cell Proliferation","volume":"10","author":"Meroni","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/0303-7207(95)03543-G","article-title":"Follicle-stimulating hormone transiently induces expression of protooncogene c-myc in primary Sertoli cell cultures of early pubertal and prepubertal rat","volume":"111","author":"Lim","year":"1995","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"E914","DOI":"10.1152\/ajpendo.00477.2011","article-title":"Signal transduction pathways in FSH regulation of rat Sertoli cell proliferation","volume":"302","author":"Riera","year":"2012","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1095\/biolreprod44.5.842","article-title":"Presence and role of c-myc proto-oncogene product in mammalian sperm cell function","volume":"44","author":"Naz","year":"1991","journal-title":"Biol. Reprod."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"e14556","DOI":"10.1111\/and.14556","article-title":"ANXA2, SP17, SERPINA5, PRDX2 genes, and sperm DNA fragmentation differentially represented in male partners of infertile couples with normal and abnormal sperm parameters","volume":"54","author":"Afsari","year":"2022","journal-title":"Andrologia"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"4374","DOI":"10.1210\/en.2006-0484","article-title":"The mouse testis is the source of various serine proteases and serine proteinase inhibitors (SERPINs): Serine proteases and SERPINs identified in Leydig cells are under gonadotropin regulation","volume":"147","author":"Odet","year":"2006","journal-title":"Endocrinology"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1210\/en.2003-0955","article-title":"Evidence for similar expression of protein C inhibitor and the urokinase-type plasminogen activator system during mouse testis development","volume":"145","author":"Odet","year":"2004","journal-title":"Endocrinology"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"484","DOI":"10.5534\/wjmh.190038","article-title":"The Role of Endoplasmic Reticulum Stress Response in Male Reproductive Physiology and Pathology: A Review","volume":"38","author":"Karna","year":"2020","journal-title":"World J. Mens. Health"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1172\/JCI2350","article-title":"Carbohydrate-deficient glycoprotein syndrome type Ib. Phosphomannose isomerase deficiency and mannose therapy","volume":"101","author":"Niehues","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"3317","DOI":"10.1182\/blood-2002-12-3656","article-title":"B-cell-specific transcription factor BACH2 modifies the cytotoxic effects of anticancer drugs","volume":"102","author":"Kamio","year":"2003","journal-title":"Blood"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1182\/blood-2005-12-040972","article-title":"Bcr-Abl signaling through the PI-3\/S6 kinase pathway inhibits nuclear translocation of the transcription factor Bach2, which represses the antiapoptotic factor heme oxygenase-1","volume":"109","author":"Yoshida","year":"2007","journal-title":"Blood"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/jemt.10312","article-title":"Contribution of epididymal secretory proteins for spermatozoa maturation","volume":"61","author":"Dacheux","year":"2003","journal-title":"Microsc. Res. Tech."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1111\/j.1439-0272.2009.00950.x","article-title":"Correlation between neutral alpha-glucosidase activity and sperm DNA fragmentation","volume":"41","author":"Watanabe","year":"2009","journal-title":"Andrologia"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"15052","DOI":"10.1038\/s41598-019-51380-w","article-title":"Insights into replicative senescence of human testicular peritubular cells","volume":"9","author":"Schmid","year":"2019","journal-title":"Sci. Rep."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/10\/1462\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:59:59Z","timestamp":1760129999000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/10\/1462"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,27]]},"references-count":152,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["biom13101462"],"URL":"https:\/\/doi.org\/10.3390\/biom13101462","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,27]]}}}