{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T23:38:46Z","timestamp":1789169926377,"version":"build-2803163510"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T00:00:00Z","timestamp":1652313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    Non-obstructive azoospermia (NOA) is the most severe form of male infertility. Currently, known causative factors, including congenital and several acquired causes only account for approximately 30% of NOA cases. The causes for NOA remain unclear for most patients, which is known as idiopathic (iNOA). However, whether iNOA is due to congenital defects or acquired abnormalities is a confusing problem due to the delayed diagnosis of this frustrating condition until the childbearing age. Therefore, we collected several cases with \u201csecondary idiopathic NOA\u201d and detected the altered mRNAs profiles in the testicular tissues to explore the possible molecular basis.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Materials and Methods:<\/jats:bold>\n                    In this study, several patients with a previous history of natural pregnancy with their partners before, who were diagnosed as iNOA based on the outcomes of routine semen analysis and multiple testis biopsies now, were enrolled. Some known risk factors and genetic factors were excluded. Therefore, we defined this phenotype as \u201csecondary idiopathic NOA.\u201d To explore the possible molecular basis of this disease, we performed mRNA expression analysis through next-generation sequencing on three cases and other three patients with obstructive azoospermia as controls. Bioinformatics analyses were conducted to assess differentially expressed genes and possible biological mechanisms involved in the disease. Quantitative real-time reverse transcription polymerase chain reaction assays were applied to confirm the results in several selected mRNAs involved in stages and metabolism of Sertoli cells.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    A series of mRNAs were found to be altered in testicular tissues between patients with \u201csecondary idiopathic NOA\u201d and controls, including 6,028 downregulated and 3,402 upregulated mRNAs. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genome (KEGG) analyses revealed a range of GO and KEGG terms, such as cellular process involved in reproduction, protein degradation, and absorption.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    The present study introduces a novel classification called \u201csecondary idiopathic NOA.\u201d We provide a global view of the altered mRNAs involved in spermatogenetic failure in these cases. Regarding the limited samples, further studies should be taken to understand this new classification.\n                  <\/jats:p>","DOI":"10.3389\/fcell.2022.824596","type":"journal-article","created":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T04:08:44Z","timestamp":1652328524000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Altered mRNAs Profiles in the Testis of Patients With \u201cSecondary Idiopathic Non-Obstructive Azoospermia\u201d"],"prefix":"10.3389","volume":"10","author":[{"given":"Dongdong","family":"Tang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuokuo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingrong","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Geng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiru","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojin","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxia","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1111\/andr.12548","article-title":"The Seminiferous Tubule Caliber Pattern as Evaluated at High Magnification during Microdissection Testicular Sperm Extraction Predicts Sperm Retrieval in Patients with Non\u2010obstructive Azoospermia","volume":"7","author":"Caroppo","year":"2019","journal-title":"Andrology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"W305","DOI":"10.1093\/nar\/gkp427","article-title":"ToppGene Suite for Gene List Enrichment Analysis and Candidate Gene Prioritization","volume":"37","author":"Chen","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"B3","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1038\/s41422-018-0074-y","article-title":"Single-cell RNA-Seq Uncovers Dynamic Processes and Critical Regulators in Mouse Spermatogenesis","volume":"28","author":"Chen","year":"2018","journal-title":"Cell Res"},{"key":"B4","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1038\/aja.2012.141","article-title":"Microdissection Testicular Sperm Extraction: an Update","volume":"15","author":"Dabaja","year":"2013","journal-title":"Asian J. 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