{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T07:55:57Z","timestamp":1782546957252,"version":"3.54.5"},"reference-count":59,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T00:00:00Z","timestamp":1666224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Centre for International Scientific Studies and Collaboration (CISSC)","award":["01DS13003"],"award-info":[{"award-number":["01DS13003"]}]},{"name":"Ministry of Science, Research and Technology","award":["01DS13003"],"award-info":[{"award-number":["01DS13003"]}]},{"DOI":"10.13039\/501100002347","name":"BMBF","doi-asserted-by":"publisher","award":["01DS13003"],"award-info":[{"award-number":["01DS13003"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Non-obstructive azoospermia (NOA) is a serious cause of male infertility. The Sertoli cell responds to androgens and takes on roles supporting spermatogenesis, which may cause infertility. This work aims to enhance the genetic diagnosis of NOA via the discovery of new and hub genes implicated in human NOA and to better assess the odds of successful sperm extraction according to the individual\u2019s genotype. Whole exome sequencing (WES) was done on three NOA patients to find key genes involved in NOA. We evaluated genome-wide transcripts (about 50,000 transcripts) by microarray between the Sertoli of non-obstructive azoospermia and normal cells. The microarray analysis of three human cases with different non-obstructive azoospermia revealed that 32 genes were upregulated, and the expressions of 113 genes were downregulated versus the normal case. For this purpose, Enrich Shiny GO, STRING, and Cytoscape online evaluations were applied to predict the functional and molecular interactions of proteins and then recognize the master pathways. The functional enrichment analysis demonstrated that the biological process (BP) terms \u201cinositol lipid-mediated signaling\u201d, \u201cpositive regulation of transcription by RNA polymerase II\u201d, and \u201cpositive regulation of DNA-templated transcription\u201d significantly changed in upregulated differentially expressed genes (DEGs). The BP investigation of downregulated DEGs highlighted \u201cmitotic cytokinesis\u201d, \u201cregulation of protein-containing complex assembly\u201d, \u201ccytoskeleton-dependent cytokinesis\u201d, and the \u201cpeptide metabolic process\u201d. Overrepresented molecular function (MF) terms in upregulated DEGs included \u201cubiquitin-specific protease binding\u201d, \u201cprotease binding\u201d, \u201cphosphatidylinositol trisphosphate phosphatase activity\u201d, and \u201cclathrin light chain binding\u201d. Interestingly, the MF analysis of the downregulated DEGs revealed overexpression in \u201cATPase inhibitor activity\u201d, \u201cglutathione transferase activity\u201d, and \u201cATPase regulator activity\u201d. Our findings suggest that these genes and their interacting hub proteins could help determine the pathophysiologies of germ cell abnormalities and infertility.<\/jats:p>","DOI":"10.3390\/ijms232012570","type":"journal-article","created":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T22:49:46Z","timestamp":1666306186000},"page":"12570","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Whole Exome Sequencing and In Silico Analysis of Human Sertoli in Patients with Non-Obstructive Azoospermia"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8246-595X","authenticated-orcid":false,"given":"Hossein","family":"Azizi","sequence":"first","affiliation":[{"name":"Faculty of Biotechnology, Amol University of Special Modern Technologies, Amol 46156-64616, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6456-1200","authenticated-orcid":false,"given":"Danial","family":"Hashemi Karoii","sequence":"additional","affiliation":[{"name":"Faculty of Biotechnology, Amol University of Special Modern Technologies, Amol 46156-64616, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4813-1213","authenticated-orcid":false,"given":"Thomas","family":"Skutella","sequence":"additional","affiliation":[{"name":"Institute for Anatomy and Cell Biology, Medical Faculty, University of Heidelberg, Im Neuenheimer Feld 307, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2486","DOI":"10.1080\/15384101.2016.1207835","article-title":"Sertoli cells are capable of proliferation into adulthood in the transition region between the seminiferous tubules and the rete testis in Wistar rats","volume":"15","author":"Figueiredo","year":"2016","journal-title":"Cell Cycle"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/978-3-319-31973-5_9","article-title":"Biology of the Sertoli cell in the fetal, pubertal, and adult mammalian testis","volume":"58","author":"Chojnacka","year":"2016","journal-title":"Mol. 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