{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T19:13:04Z","timestamp":1776280384485,"version":"3.50.1"},"reference-count":174,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"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. Endocrinol."],"abstract":"<jats:p>Sertoli Cells-Only Syndrome (SCOS), also known as Del Castillo syndrome or germ cell aplasia, is the most frequent cause of non-obstructive azoospermia, being found in 26-57% of patients affected by this condition. Although up to 10% of infertile males seeking medical attention are affected by SCOS and almost 80 years have already passed since this challenging syndrome was first described, therapeutic approaches to date are modest. The etiology of SCOS involves a large number of causes, including Y-chromosome microdeletions, trauma, viral infections, exposure to radiation or toxins, or idiopathic causes. The seminiferous tubule may be involved in its entirety or affected in a focal pattern only, with residual islands of spermatogenesis, which explains the variability in the success rate of sperm recovery in these patients. No prognostic markers, hormonal or of other nature, are currently employed in clinical practice. The purpose of this review is to organize the known information on SCOS and define current correct diagnostic and clinical practice, focusing in the second section on areas of research to look out for in terms of potential practical developments from the vast knowledge accumulated over recent decades.<\/jats:p>","DOI":"10.3389\/fendo.2025.1715642","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T05:17:57Z","timestamp":1766121477000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Sertoli cells-only syndrome: current clinical approaches and ongoing research trends"],"prefix":"10.3389","volume":"16","author":[{"given":"Elena","family":"Eugeni","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iva","family":"Arato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Mancuso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Brancorsini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Luca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sieglinde","family":"Kofler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,19]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","DOI":"10.1016\/S0140-6736(20)32667-2","article-title":"Male infertility","volume":"397","author":"Agarwal","year":"2021","journal-title":"Lancet"},{"key":"B2","volume-title":"Infertility- Fact Sheet","year":"2024"},{"key":"B3","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.fertnstert.2020.11.015","article-title":"Diagnosis and treatment of infertility in men: AUA\/ASRM guideline part I","volume":"115","author":"Schlegel","year":"2021","journal-title":"Fertil Steril"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s10815-021-02063-x","article-title":"Sertoli cell-only syndrome: etiology and clinical management","volume":"38","author":"Gashti","year":"2021","journal-title":"J Assist Reprod Genet"},{"key":"B5","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1093\/humrep\/del279","article-title":"Histological evaluation of the human testis\u2014approaches to optimizing the clinical value of the assessment: Mini Review","volume":"22","author":"McLachlan","year":"2007","journal-title":"Hum Reprod"},{"key":"B6","article-title":"Syndrome produced by absence of the germinal epithelium without impairment of the Sertoli or leydig cells","volume":"7","author":"Del Castillo","year":"1947","journal-title":"J Clin Endocrinol Metab"},{"key":"B7","doi-asserted-by":"crossref","first-page":"470","DOI":"10.3390\/ijms20030470","article-title":"Identification of premeiotic, meiotic, and postmeiotic cells in testicular biopsies without sperm from Sertoli cell-only syndrome patients","volume":"20","author":"Abofoul-Azab","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2605.1991.tb01073.x","article-title":"Morphological evidence for two types of idiopathic \u2018Sertoli-cell-only\u2019 syndrome","volume":"14","author":"Terada","year":"1991","journal-title":"Int J Androl"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/15.11.2269","article-title":"Criteria predicting the absence of spermatozoa in the Sertoli cell-only syndrome can be used to improve success rates of sperm retrieval","volume":"15","author":"Anniballo","year":"2000","journal-title":"Hum Reprod"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod17.1.108","article-title":"Pathophysiological observations of Sertoli cells in patients with germinal aplasia or severe germ cell depletion. 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