{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T05:52:53Z","timestamp":1776232373529,"version":"3.50.1"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The maintenance of mammalian spermatogenesis depends on the intricate molecular and cellular interactions between spermatogonial stem cells and their cognate niche in the seminiferous epithelium of the testis. To sustain the continuous production of sperm, spermatogonia proliferate and differentiate under the control of various niche factors, promoting either self-renewal or commitment to spermatogonial differentiation. Single-cell RNA sequencing analyses have identified different subpopulations of spermatogonia in primates based on the expression of specific marker genes (PIWIL4, GFRA1, NANOS3, and KIT). However, the spatial distribution of the different spermatogonial subpopulations and their relationship with the niche has not been described yet. Here, we investigate the topological localization of spermatogonia in primates. To this end, immunohistochemical stainings for PIWIL4, GFRA1, NANOS3 and KIT were performed on Bouin fixed samples of Macaca fascicularis and quantitatively analyzed. Strauss linear selectivity index (Linear Index, Li) was employed to assess the regional distribution of spermatogonial subpopulations in the basal compartment of seminiferous tubules. Remarkably, PIWIL4+ spermatogonia showed a random distribution along the basal compartment across all the stages of the seminiferous epithelium cycle. In contrast, GFRA1+, NANOS3+, and KIT+ spermatogonia displayed stage-dependent localization patterns. The spatial organization of different spermatogonial subpopulations, appeared coordinated with the cycle of the seminiferous epithelium, suggesting a dynamic regulation of spermatogonial behavior throughout the process of sperm production. Our study contributes to the growing body of literature aimed at deciphering the complexities of SSC biology and the regulation of spermatogenesis in mammalian species, with implications for understanding male fertility.<\/jats:p>","DOI":"10.1093\/biolre\/ioag018","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T12:23:13Z","timestamp":1768825393000},"page":"1498-1506","source":"Crossref","is-referenced-by-count":0,"title":["The topographical distribution of spermatogonial subpopulations during the cycle of seminiferous epithelium in\n                    <i>Macaca Fascicularis<\/i>"],"prefix":"10.1093","volume":"114","author":[{"given":"Martina","family":"Palazzoli","sequence":"first","affiliation":[{"name":"Department of Anatomy, Histology, Forensic Medicine and Orthopedic, Section of Histology, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Capponi","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology, Forensic Medicine and Orthopedic, Section of Histology, Sapienza University of Rome, 00161 Rome, Italy"},{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego , La Jolla, CA ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Di Persio","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology, Forensic Medicine and Orthopedic, Section of Histology, Sapienza University of Rome, 00161 Rome, Italy"},{"name":"Centre of Reproductive Medicine and Andrology, University Hospital M\u00fcnster , 48149 M\u00fcnster ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Fera","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology, Forensic Medicine and Orthopedic, Section of Histology, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Filippini","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology, Forensic Medicine and Orthopedic, Section of Histology, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7571-5313","authenticated-orcid":false,"given":"Stefan","family":"Schlatt","sequence":"additional","affiliation":[{"name":"Centre of Reproductive Medicine and Andrology, University Hospital M\u00fcnster , 48149 M\u00fcnster ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0181-6194","authenticated-orcid":false,"given":"Nina","family":"Neuhaus","sequence":"additional","affiliation":[{"name":"Centre of Reproductive Medicine and Andrology, University Hospital M\u00fcnster , 48149 M\u00fcnster ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0399-0145","authenticated-orcid":false,"given":"Elena","family":"Vicini","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology, Forensic Medicine and Orthopedic, Section of Histology, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"2026041501020340500_ref1","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.stem.2023.12.006","article-title":"Hallmarks of stemness in mammalian tissues","volume":"31","author":"Beumer","year":"2024","journal-title":"Cell Stem Cell"},{"key":"2026041501020340500_ref2","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1111\/dgd.12574","article-title":"Open niche regulation of mouse spermatogenic stem cells","volume":"60","author":"Yoshida","year":"2018","journal-title":"Develop Growth Differ"},{"key":"2026041501020340500_ref3","doi-asserted-by":"publisher","first-page":"R169","DOI":"10.1530\/REP-18-0476","article-title":"Molecular regulation of spermatogonial stem cell renewal and differentiation","volume":"158","author":"M\u00e4kel\u00e4","year":"2019","journal-title":"Reproduction"},{"key":"2026041501020340500_ref4","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1095\/biolreprod65.4.1179","article-title":"Distribution of type a Spermatogonia in the mouse is not Random1","volume":"65","author":"Chiarini-Garcia","year":"2001","journal-title":"Biol Reprod"},{"key":"2026041501020340500_ref5","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1126\/science.1144885","article-title":"A vasculature-associated niche for undifferentiated Spermatogonia in the mouse testis","volume":"317","author":"Yoshida","year":"2007","journal-title":"Science"},{"key":"2026041501020340500_ref6","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.stem.2018.11.013","article-title":"Competition for mitogens regulates Spermatogenic stem cell homeostasis in an open niche","volume":"24","author":"Kitadate","year":"2019","journal-title":"Cell Stem Cell"},{"key":"2026041501020340500_ref7","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1101\/gad.240465.114","article-title":"Functional and molecular features of the Id4+ germline stem cell population in mouse testes","volume":"28","author":"Chan","year":"2014","journal-title":"Genes Dev"},{"key":"2026041501020340500_ref8","doi-asserted-by":"crossref","first-page":"108424","DOI":"10.1016\/j.isci.2023.108424","article-title":"The hypoxia-inducible factor EPAS1 is required for spermatogonial stem cell function in regenerative conditions","volume":"26","author":"Bernstein","year":"2023","journal-title":"iScience"},{"key":"2026041501020340500_ref9","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/j.devcel.2020.01.014","article-title":"Metabolic changes accompanying Spermatogonial stem cell differentiation","volume":"52","author":"Lord","year":"2020","journal-title":"Dev Cell"},{"key":"2026041501020340500_ref10","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1530\/REP-19-0254","article-title":"A subpopulation of human Adark spermatogonia behaves as the reserve stem cell","volume":"159","author":"Caldeira-Brant","year":"2020","journal-title":"Reproduction"},{"key":"2026041501020340500_ref11","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1016\/j.devcel.2020.05.010","article-title":"Single-cell RNA sequencing of human, macaque, and mouse testes uncovers conserved and divergent features of mammalian spermatogenesis","volume":"54","author":"Shami","year":"2020","journal-title":"Dev Cell"},{"key":"2026041501020340500_ref12","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1016\/j.devcel.2020.07.018","article-title":"Single-cell RNA sequencing of the Cynomolgus macaque testis reveals conserved transcriptional profiles during mammalian spermatogenesis","volume":"54","author":"Lau","year":"2020","journal-title":"Dev Cell"},{"key":"2026041501020340500_ref13","doi-asserted-by":"publisher","first-page":"1631","DOI":"10.1084\/jem.20161371","article-title":"A transit-amplifying population underpins the efficient regenerative capacity of the testis","volume":"214","author":"Carrieri","year":"2017","journal-title":"J Exp Med"},{"key":"2026041501020340500_ref14","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1038\/s41422-018-0099-2","article-title":"The adult human testis transcriptional cell atlas","volume":"28","author":"Guo","year":"2018","journal-title":"Cell Res"},{"key":"2026041501020340500_ref15","doi-asserted-by":"publisher","first-page":"1501","DOI":"10.1016\/j.celrep.2019.01.045","article-title":"The neonatal and adult human testis defined at the single-cell level","volume":"26","author":"Sohni","year":"2019","journal-title":"Cell Rep"},{"key":"2026041501020340500_ref16","doi-asserted-by":"crossref","first-page":"100395","DOI":"10.1016\/j.xcrm.2021.100395","article-title":"Single-cell RNA-seq unravels alterations of the human spermatogonial stem cell compartment in patients with impaired spermatogenesis","volume":"2","author":"Di Persio","year":"2021","journal-title":"Cell Reports Medicine"},{"key":"2026041501020340500_ref17","doi-asserted-by":"publisher","first-page":"dev201430","DOI":"10.1242\/dev.201430","article-title":"Interplay of spermatogonial subpopulations during initial stages of spermatogenesis in adult primates","volume":"150","author":"Capponi","year":"2023","journal-title":"Development"},{"key":"2026041501020340500_ref18","doi-asserted-by":"publisher","first-page":"3430","DOI":"10.1242\/dev.150284","article-title":"Spermatogonial kinetics in humans","volume":"144","author":"Di Persio","year":"2017","journal-title":"Development"},{"key":"2026041501020340500_ref19","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1126\/science.287.5457.1489","article-title":"Regulation of cell fate decision of undifferentiated Spermatogonia by GDNF","volume":"287","author":"Meng","year":"2000","journal-title":"Science"},{"key":"2026041501020340500_ref20","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1095\/biolreprod.103.015925","article-title":"Organization of Seminiferous Epithelium in primates: relationship to Spermatogenic efficiency, phylogeny, and mating System1","volume":"69","author":"Wistuba","year":"2003","journal-title":"Biol Reprod"},{"key":"2026041501020340500_ref21","doi-asserted-by":"publisher","first-page":"3043","DOI":"10.1002\/stem.206","article-title":"Identification of Spermatogonial stem cell subsets by morphological analysis and prospective isolation","volume":"27","author":"Grisanti","year":"2009","journal-title":"Stem Cells"},{"key":"2026041501020340500_ref22","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/s00418-016-1478-8","article-title":"Identification of sperm equatorial segment protein 1 in the acrosome as the primary binding target of peanut agglutinin (PNA) in the mouse testis","volume":"147","author":"Nakata","year":"2017","journal-title":"Histochem Cell Biol"},{"key":"2026041501020340500_ref23","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.113.111682","article-title":"Novel stage classification of human spermatogenesis based on acrosome Development1","volume":"89","author":"Muciaccia","year":"2013","journal-title":"Biol Reprod"},{"key":"2026041501020340500_ref24","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1530\/rep.0.1260669","article-title":"Non-random distribution of spermatogonia in rats: evidence of niches in the seminiferous tubules","volume":"126","author":"Chiarini-Garcia","year":"2003","journal-title":"Reproduction"},{"key":"2026041501020340500_ref25","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1577\/1548-8659(1979)108<344:REFIEI>2.0.CO;2","article-title":"Reliability estimates for Ivlev\u2019s electivity index, the forage ratio, and a proposed linear index of food selection","volume":"108","author":"Strauss","year":"1979","journal-title":"Trans Am Fish Soc"},{"key":"2026041501020340500_ref26","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1093\/humrep\/deae013","article-title":"Identification of two hidden clinical subgroups among men with idiopathic cryptozoospermia","volume":"39","author":"Sch\u00fclke","year":"2024","journal-title":"Hum Reprod"},{"key":"2026041501020340500_ref27","doi-asserted-by":"publisher","first-page":"bio059146","DOI":"10.1242\/bio.059146","article-title":"NANOS3 suppresses premature spermatogonial differentiation to expand progenitors and fine-tunes spermatogenesis in mice","volume":"11","author":"Inoue","year":"2022","journal-title":"Biology Open"},{"key":"2026041501020340500_ref28","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1016\/j.ydbio.2009.10.002","article-title":"The heterogeneity of spermatogonia is revealed by their topology and expression of marker proteins including the germ cell-specific proteins Nanos2 and Nanos3","volume":"336","author":"Suzuki","year":"2009","journal-title":"Dev Biol"}],"container-title":["Biology of Reproduction"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/biolreprod\/advance-article-pdf\/doi\/10.1093\/biolre\/ioag018\/66510910\/ioag018.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/biolreprod\/article-pdf\/114\/4\/1498\/66510910\/ioag018.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/biolreprod\/article-pdf\/114\/4\/1498\/66510910\/ioag018.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T05:02:07Z","timestamp":1776229327000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/biolreprod\/article\/114\/4\/1498\/8435249"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,21]]},"references-count":28,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,1,21]]},"published-print":{"date-parts":[[2026,4,13]]}},"URL":"https:\/\/doi.org\/10.1093\/biolre\/ioag018","relation":{},"ISSN":["0006-3363","1529-7268"],"issn-type":[{"value":"0006-3363","type":"print"},{"value":"1529-7268","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,4]]},"published":{"date-parts":[[2026,1,21]]}}}