{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T12:11:03Z","timestamp":1783512663478,"version":"3.55.0"},"reference-count":50,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,7,28]],"date-time":"2024-07-28T00:00:00Z","timestamp":1722124800000},"content-version":"vor","delay-in-days":27,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Reproduction Devel"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Clusterin (CLU), one of the main glycoproteins in mammalian semen and the male reproductive tract, plays a role in spermatogenesis and sperm maturation. Given the poor reliability of classic seminal studies in determining male\u2010fertilizing capacity and the differences in CLU abundance between normal and abnormal spermatozoa, we investigated the potential value of <jats:italic>mRNA\u2010CLU<\/jats:italic> levels and protein distribution in spermatozoa as markers of sperm quality and predictors of male fertility. This multicenter study included 90 patients undergoing in vitro fertilization (IVF) treatment with their partners, and a control group of 36 fertile males with normal seminograms. We assessed the relationship between IVF treatment outcomes, seminogram variables, <jats:italic>mRNA\u2010CLU<\/jats:italic> levels by\u00a0quantitative real\u2010time\u2010PCR and CLU distribution by immunostaining in spermatozoa. Our study reveals CLU staining in the acrosome (<jats:italic>p<\/jats:italic>\u2009=\u20090.002, OR 14.8, 95% CI: 2.7\u201379.3) and <jats:italic>mRNA\u2010CLU<\/jats:italic> levels (<jats:italic>p<\/jats:italic>\u2009=\u20090.005, OR 10.85, 95% CI: 2.0\u201357.4) as independent risk factors for pregnancy failure, irrespective of traditional seminogram variables. Additionally, our results suggest that CLU, and specially its secreted isoform, constitutes a component of the protein pool that human spermatozoa can produce during its maturation process, exhibiting a variable abundance and distribution in spermatozoa from fertile men compared to those in patients with altered seminograms and infertile patients with normal seminograms. Our study is the first to identify <jats:italic>mRNA\u2010CLU<\/jats:italic> levels and CLU immunostaining in the spermatozoa acrosome as independent risk factors for pregnancy failure, with distribution patterns correlating with sperm maturity and seminogram alterations.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mrd.23764","type":"journal-article","created":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T04:39:03Z","timestamp":1722227943000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Clusterin <b>expression<\/b> and distribution in spermatozoa as predictor of male fertility"],"prefix":"10.1002","volume":"91","author":[{"given":"Mar\u00eda","family":"Hern\u00e1ndez\u2010Herrador","sequence":"first","affiliation":[{"name":"Reproduction Unit Hospital Universitario Costa del Sol  Marbella Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garc\u00eda\u2010Aranda","family":"Marilina","sequence":"additional","affiliation":[{"name":"Research and Innovation Unit Hospital Universitario Costa del Sol  Marbella Spain"},{"name":"Surgical Specialties, Biochemistry, Molecular Biology and Immunology Department, Faculty of Medicine Malaga University  Malaga Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga (IBIMA)\u2010Plataforma Bionand Research Institute Malaga Spain"},{"name":"Research Network on Chronicity, Primary Care and Health Promotion (RICAPPS)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Luisa Hortas","sequence":"additional","affiliation":[{"name":"Clinical Laboratories Area Hospital Universitario Costa del Sol Marbella Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Carrillo\u2010Lucena","sequence":"additional","affiliation":[{"name":"Reproduction Unit Hospital Universitario Costa del Sol  Marbella Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaira","family":"Caracuel","sequence":"additional","affiliation":[{"name":"Research and Innovation Unit Hospital Universitario Costa del Sol  Marbella Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Antonio","family":"Castilla\u2010Alcal\u00e1","sequence":"additional","affiliation":[{"name":"Reproduction Unit (Clinical Laboratory and Obstetrics and Gynecology Clinical Management Units) Hospital Universitario Virgen de las Nieves Granada Spain"},{"name":"Instituto de Investigaci\u00f3n Biosanitaria (ibs.GRANADA) Research Institute Universidad de Granada Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desir\u00e9e","family":"Mart\u00edn\u2010Garc\u00eda","sequence":"additional","affiliation":[{"name":"Research and Innovation Unit Hospital Universitario Costa del Sol  Marbella Spain"},{"name":"Surgical Specialties, Biochemistry, Molecular Biology and Immunology Department, Faculty of Medicine Malaga University  Malaga Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga (IBIMA)\u2010Plataforma Bionand Research Institute Malaga Spain"},{"name":"Research Network on Chronicity, Primary Care and Health Promotion (RICAPPS)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximino","family":"Redondo","sequence":"additional","affiliation":[{"name":"Research and Innovation Unit Hospital Universitario Costa del Sol  Marbella Spain"},{"name":"Surgical Specialties, Biochemistry, Molecular Biology and Immunology Department, Faculty of Medicine Malaga University  Malaga Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga (IBIMA)\u2010Plataforma Bionand Research Institute Malaga Spain"},{"name":"Research Network on Chronicity, Primary Care and Health Promotion (RICAPPS)"},{"name":"REDISSEC (Health Research on Chronic Patients Network)"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,28]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M302157200"},{"key":"e_1_2_12_3_1","volume-title":"Fundamentos de reproducci\u00f3n","author":"Arenas J. M. B.","year":"2009"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/713688946"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dem016"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.965076"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2013.01.124"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1939-4640.2004.tb02844.x"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2011.12.036"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmy017"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M608162200"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.theriogenology.2010.04.023"},{"key":"e_1_2_12_13_1","unstructured":"De Fertilidad S. E.2011.Libro Blanco Sociosanitario: \u201cLa Infertilidad en Espa\u00f1a: Situaci\u00f3n Actual y Perspectivas\u201d.Sociedad Espa\u00f1ola de Fertilidad."},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117043"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/and.12558"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389203718666170918155247"},{"key":"e_1_2_12_17_1","unstructured":"Garcia\u2010Herrero S. Garrido N. &Martinez\u2010Conejero J.Microarray analysis of infertile males in absence of abnormal sperm count reveals profound expression changes in spermatogenesis related gene products.2nd International IVI Congress Barcelona (Spain) 2007."},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2013.02.006"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.108.075739"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0272.2005.00656.x"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2007.11.015"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2011.12.035"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10815-012-9779-x"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/4.7.673"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1939-4640.2001.tb02594.x"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.23340"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.108.072843"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-2725(01)00155-8"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1071\/RD18124"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2013.01.111"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209233200"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/den024"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.1080300109"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/and.13498"},{"key":"e_1_2_12_35_1","first-page":"44","article-title":"Indicadores de calidad basados en el estado del arte. ponencia","volume":"29","author":"Moreno J. M.","year":"2012","journal-title":"XXIX Congreso de la Sociedad Espa\u00f1ola de Fertilidad. Revista Iberoamericana de Fertilidad"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114594"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.humrep.a138736"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.4103\/1008-682X.122198"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2011.03.059"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/360986"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1262\/jrd.2016-093"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.9.2262"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod66.4.1061"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7827-11-48"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod45.1.195"},{"key":"e_1_2_12_46_1","first-page":"355","article-title":"Current evaluation of male infertility","volume":"45","author":"Teppa\u2010Garr\u00e1n A. D.","year":"2004","journal-title":"Investigacion Clinica"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ucl.2013.08.006"},{"key":"e_1_2_12_48_1","volume-title":"WHO","author":"World Health Organization","year":"2010"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.11.5907"},{"issue":"218","key":"e_1_2_12_50_1","first-page":"218","article-title":"Leydig cell apoptosis and its regulation","volume":"9","author":"Yuan S. H.","year":"2003","journal-title":"Zhonghua nan ke xue = National journal of andrology"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2012.06.012"}],"container-title":["Molecular Reproduction and Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mrd.23764","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T04:55:09Z","timestamp":1722228909000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mrd.23764"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7]]},"references-count":50,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["10.1002\/mrd.23764"],"URL":"https:\/\/doi.org\/10.1002\/mrd.23764","archive":["Portico"],"relation":{},"ISSN":["1040-452X","1098-2795"],"issn-type":[{"value":"1040-452X","type":"print"},{"value":"1098-2795","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7]]},"assertion":[{"value":"2024-02-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e23764"}}