{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T18:27:08Z","timestamp":1778869628042,"version":"3.51.4"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2022,8,19]],"date-time":"2022-08-19T00:00:00Z","timestamp":1660867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100003086","name":"Basque Government","doi-asserted-by":"publisher","award":["GIC12\/173"],"award-info":[{"award-number":["GIC12\/173"]}],"id":[{"id":"10.13039\/501100003086","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003451","name":"University of the Basque Country","doi-asserted-by":"publisher","award":["EHUA14\/17"],"award-info":[{"award-number":["EHUA14\/17"]}],"id":[{"id":"10.13039\/501100003451","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>STUDY QUESTION<\/jats:title>\n                  <jats:p>Is there a relationship between human sperm aminopeptidase N (APN) and embryo development in humans?<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>SUMMARY ANSWER<\/jats:title>\n                  <jats:p>Human sperm APN could possibly become a new molecular biomarker for identifying the potential for high-quality and usable embryos.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>WHAT IS KNOWN ALREADY<\/jats:title>\n                  <jats:p>The diagnosis of male fertility is one of the major concerns of reproductive medicine. Approximately 30\u201340% of men with otherwise normal fertility parameters are still unable to achieve pregnancy. The predictive clinical value of semen analysis to identify fertile or infertile males is limited; therefore, new diagnostic methodologies for sperm are urgently required. Sperm APN may be a relevant molecular marker due to its high concentration in sperm cells and its important roles in sperm physiology, such as its functions in motility, acrosome reaction and embryo development.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>STUDY DESIGN, SIZE, DURATION<\/jats:title>\n                  <jats:p>This study included 81 couples who underwent oocyte-donation cycles at Cl\u00ednica IVI Bilbao (Spain), yielding 611 embryos, between September 2014 and July 2015.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n                  <jats:p>This study was conducted in an assisted reproduction unit and an academic research laboratory. All the semen samples were examined and classified following World Health Organization guidelines. Spermatozoa were isolated from semen using the discontinuous colloidal silica gradient (45\u201390%) technique. Embryo quality and development were determined according to the Spanish Association of Reproduction Biology Studies (ASEBIR) criteria. Human sperm APN levels were analyzed by quantitative and semiquantitative flow cytometry.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n                  <jats:p>The most well-developed and usable blastocysts were associated with low sperm APN levels. Semen samples that had lower APN levels generated more expanded, hatched and usable blastocysts and fewer early, arrested and non-usable blastocysts. The cumulative probability of having well-developed blastocysts increased by 1.38-fold at Day 5 and 1.90-fold at Day 6 of embryo development, and the likelihood of having usable embryos increased by 1.48-fold, when semen samples with low APN levels were used during the ICSI technique.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n                  <jats:p>The data were obtained from a single fertility clinic. A multicentre study will be required to confirm the results.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n                  <jats:p>Human sperm APN has the potential to become a new molecular biomarker to help identify the potential for high-quality embryos and diagnose male infertility, especially when seminal parameters are close to the threshold values. It could be a crucial tool for couples for whom the number of usable blastocysts is critical for ART success.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>STUDY FUNDING\/COMPETING INTEREST(S)<\/jats:title>\n                  <jats:p>This study was supported by grants from the Basque Government (GIC15\/165) and the University of the Basque Country (UPV\/EHU) (EHUA14\/17). The authors declare that they have no conflicts of interest.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>TRIAL REGISTRATION NUMBER<\/jats:title>\n                  <jats:p>N\/A.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/humrep\/deac170","type":"journal-article","created":{"date-parts":[[2022,8,19]],"date-time":"2022-08-19T13:36:13Z","timestamp":1660916173000},"page":"2246-2254","source":"Crossref","is-referenced-by-count":3,"title":["Sperm aminopeptidase N identifies the potential for high-quality blastocysts and viable embryos in oocyte-donation cycles"],"prefix":"10.1093","volume":"37","author":[{"given":"Marta","family":"Gianzo","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medicine and Nursery, University of the Basque Country (UPV\/EHU), Leioa , Bizkaia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Itziar","family":"Urizar-Arenaza","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine and Nursery, University of the Basque Country (UPV\/EHU), Leioa , Bizkaia, Spain"},{"name":"Innovation in Assisted Reproduction Group, Biocruces-Bizkaia Health Research Institute , Barakaldo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iraia","family":"Mu\u00f1oa-Hoyos","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine and Nursery, University of the Basque Country (UPV\/EHU), Leioa , Bizkaia, Spain"},{"name":"Innovation in Assisted Reproduction Group, Biocruces-Bizkaia Health Research Institute , Barakaldo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4611-2502","authenticated-orcid":false,"given":"Gorka","family":"Labaka","sequence":"additional","affiliation":[{"name":"Hitz Center, Ixa, University of the Basque Country (UPV\/EHU), Donostia-San Sebastian , Gipuzkoa, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zaloa","family":"Larreategui","sequence":"additional","affiliation":[{"name":"Valencian Institute of Infertility (IVI-RMA)-Bilbao , Bizkaia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicol\u00e1s","family":"Garrido","sequence":"additional","affiliation":[{"name":"IVI Foundation, Instituto de Investigaci\u00f3n Sanitaria La Fe (IIS La Fe) , Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jon","family":"Irazusta","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine and Nursery, University of the Basque Country (UPV\/EHU), Leioa , Bizkaia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9202-1287","authenticated-orcid":false,"given":"Nerea","family":"Subir\u00e1n","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine and Nursery, University of the Basque Country (UPV\/EHU), Leioa , Bizkaia, Spain"},{"name":"Innovation in Assisted Reproduction Group, Biocruces-Bizkaia Health Research Institute , Barakaldo, Spain"},{"name":"MEPROlife, Medical Reproductive Solutions, Research and Development Department, Donostia-San Sebasti\u00e1n , Gipuzkoa, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,8,19]]},"reference":[{"key":"2022100305590143200_deac170-B1","first-page":"1270","article-title":"The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting","volume-title":"Hum Reprod","author":"Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology","year":"2011"},{"key":"2022100305590143200_deac170-B2","doi-asserted-by":"crossref","first-page":"890","DOI":"10.2164\/jandrol.106.000703","article-title":"Protamine levels vary between individual sperm cells of infertile human males and correlate with viability and DNA integrity","volume":"27","author":"Aoki","year":"2006","journal-title":"J Androl"},{"key":"2022100305590143200_deac170-B3","volume-title":"Cuadernos de Embriolog\u00eda Cl\u00ednica II. 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