{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:53:43Z","timestamp":1790142823072,"version":"4.0.1"},"reference-count":64,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T00:00:00Z","timestamp":1686528000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["DTS18\/00101"],"award-info":[{"award-number":["DTS18\/00101"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002809","name":"Generalitat de Catalunya","doi-asserted-by":"publisher","award":["2017SGR191"],"award-info":[{"award-number":["2017SGR191"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002809","name":"Generalitat de Catalunya","doi-asserted-by":"publisher","award":["2021SGR052"],"award-info":[{"award-number":["2021SGR052"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Non\u2010invasive molecular biomarkers for classifying azoospermia by origin into either obstructive or non\u2010obstructive\/secretory azoospermia, as well as for inferring the spermatogenic reserve of the testis of non\u2010obstructive\/secretory azoospermia patients, are of great interest for testicular sperm retrieval outcome prediction for assisted reproduction. Prior analyses of semen small non\u2010coding RNA expression in azoospermia have focused on microRNAs, but there has been a lack of attention on other regulatory small RNA species. In this regard, studying more in\u2010depth expression changes of small non\u2010coding RNA subtypes in small extracellular vesicles from semen of azoospermic individuals could be useful to select additional non\u2010invasive biomarkers with diagnostic\/prognostic purposes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and methods<\/jats:title><jats:p>A high\u2010throughput small RNA profiling analysis to determine the expression pattern of seminal small extracellular vesicle microRNAs (analyzed at the isomiR level), PIWI\u2010interacting RNAs, and transfer RNA\u2010derived small RNAs in normozoospermic (<jats:italic>n<\/jats:italic> = 4) and azoospermic (obstructive azoospermia because of pathological occurring obstruction in the genital tract, <jats:italic>n<\/jats:italic> = 4; secretory azoospermic individuals with positive testicular sperm extraction value, <jats:italic>n<\/jats:italic> = 5; secretory azoospermic individuals with negative testicular sperm extraction value, <jats:italic>n<\/jats:italic> = 4) individuals was carried out. Reverse transcriptase\u2010quantitative real\u2010time polymerase chain reaction validation analysis of selected microRNAs was additionally performed in a larger number of individuals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and discussion<\/jats:title><jats:p>Clinically relevant quantitative changes in the small non\u2010coding RNA levels contained in semen small extracellular vesicles can be used as biomarkers for the origin of azoospermia and for predicting the presence of residual spermatogenesis. In this regard, canonical isoform microRNAs (<jats:italic>n<\/jats:italic> = 185) but also other isomiR variants (<jats:italic>n<\/jats:italic> = 238) stand out in terms of numbers and fold\u2010change differences in expression, underlining the need to consider isomiRs when investigating microRNA\u2010based regulation. Conversely, although transfer RNA\u2010derived small RNAs are shown in our study to represent a high proportion of small non\u2010coding RNA sequences in seminal small extracellular vesicle samples, they are not able to discriminate the origin of azoospermia. PIWI\u2010interacting RNA cluster profiles and individual PIWI\u2010interacting RNAs with significant differential expression were also not able to discriminate. Our study demonstrated that expression values of individual and\/or combined canonical isoform microRNAs (miR\u201010a\u20105p, miR\u2010146a\u20105p, miR\u201031\u20105p, miR\u2010181b\u20105p; area under the receiver operating characteristic curve &gt;0.8) in small extracellular vesicles provide considerable clinical value in identifying samples with a high likelihood of sperm retrieval while discriminating azoospermia by origin. Although no individual microRNA showed sufficient discriminating power on its own to identify severe spermatogenic disorders with focal spermatogenesis, multivariate microRNA models in semen small extracellular vesicles have the potential to identify those individuals with residual spermatogenesis. Availability and adoption of such non\u2010invasive molecular biomarkers would represent a great improvement in reproductive treatment decision protocols for azoospermia in clinical practice.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.13461","type":"journal-article","created":{"date-parts":[[2023,5,28]],"date-time":"2023-05-28T03:54:49Z","timestamp":1685246089000},"page":"137-156","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Seminal extracellular vesicle sncRNA sequencing reveals altered miRNA\/isomiR profiles as sperm retrieval biomarkers for azoospermia"],"prefix":"10.1111","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4579-5452","authenticated-orcid":false,"given":"Sara","family":"Larriba","sequence":"first","affiliation":[{"name":"Human Molecular Genetics Group\u2010Bellvitge Biomedical Research Institute (IDIBELL)  Hospitalet de Llobregat Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Francisco","family":"S\u00e1nchez\u2010Herrero","sequence":"additional","affiliation":[{"name":"High Content Genomics and Bioinformatics (HCGB)\u2010Germans Trias I Pujol Research Institute (IGTP)  Badalona Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Pluvinet","sequence":"additional","affiliation":[{"name":"High Content Genomics and Bioinformatics (HCGB)\u2010Germans Trias I Pujol Research Institute (IGTP)  Badalona Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"L\u00f3pez\u2010Rodrigo","sequence":"additional","affiliation":[{"name":"Laboratory of Andrology and Sperm Bank Andrology Service\u2010Fundaci\u00f3 Puigvert  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Llu\u00eds","family":"Bassas","sequence":"additional","affiliation":[{"name":"Laboratory of Andrology and Sperm Bank Andrology Service\u2010Fundaci\u00f3 Puigvert  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauro","family":"Sumoy","sequence":"additional","affiliation":[{"name":"High Content Genomics and Bioinformatics (HCGB)\u2010Germans Trias I Pujol Research Institute (IGTP)  Badalona Barcelona 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