{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:00:46Z","timestamp":1785416446806,"version":"3.56.0"},"reference-count":84,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wuhan Municipal Health Commission","award":["WX23A47"],"award-info":[{"award-number":["WX23A47"]}]},{"award":["WX23A47"],"award-info":[{"award-number":["WX23A47"]}],"id":[{"id":"https:\/\/ror.org\/04jjn5s14","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Hubei Clinical Research Center for Reproductive Medicine","award":["2025RMOF007"],"award-info":[{"award-number":["2025RMOF007"]}]},{"name":"Health-related Scientific and Technological Project Program","award":["YTWS20250105"],"award-info":[{"award-number":["YTWS20250105"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Azoospermia represents the most severe manifestation of male infertility and is classified into obstructive azoospermia (OA) and non-obstructive azoospermia (NOA). NOA patients experience a lack of sperm due to testicular dysfunction, posing significant challenges in clinical diagnosis and treatment. Recent advancements in molecular biology and high-throughput technologies have led to the discovery and validation of numerous biomarkers, including proteins, non-coding RNAs, genetic polymorphisms, and imaging indicators, which have greatly enhanced the understanding of the pathophysiological mechanisms of azoospermia and facilitated non-invasive diagnostic approaches. This review aims to systematically summarize the pathogenesis of azoospermia and critically evaluate the latest advancements in diagnostic and prognostic biomarkers, including small RNAs, proteomic profiles, genetic markers, and imaging features. The overarching goal is to synthesize this knowledge toward the development of integrated, biomarker-guided strategies for precise diagnosis, prognosis prediction, and improved clinical management of azoospermia, particularly NOA.<\/jats:p>","DOI":"10.3390\/biom16060877","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:49:42Z","timestamp":1781743782000},"page":"877","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Research Progress on the Pathogenesis and Diagnostic Biomarkers of Azoospermia"],"prefix":"10.3390","volume":"16","author":[{"given":"Jiazhen","family":"Zou","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Southern University of Science and Technology Yantian Hospital, Shenzhen 518000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huihui","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China"},{"name":"Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingdan","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Southern University of Science and Technology Yantian Hospital, Shenzhen 518000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4133-7476","authenticated-orcid":false,"given":"Peng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China"},{"name":"Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4692-4300","authenticated-orcid":false,"given":"Heran","family":"Cao","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Male Reproduction and Genetics, Guangdong Provincial Reproductive Science Institute, Guangzhou 510600, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101048","DOI":"10.1016\/j.repbio.2025.101048","article-title":"Summarizing the human genes and their variants causative of non-obstructive azoospermia uncovered using whole genome\/exome sequencing","volume":"25","author":"Ibrahim","year":"2025","journal-title":"Reprod. 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