{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T07:09:58Z","timestamp":1768633798331,"version":"3.49.0"},"reference-count":61,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T00:00:00Z","timestamp":1725494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Klinefelter Syndrome Physiopathology"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,1]]},"abstract":"Abstract<\/jats:title>\n \n STUDY QUESTION<\/jats:title>\n Are Sertoli cells (SCs) from adult Klinefelter men (47,XXY) capable of proliferating in vitro and maintaining their main phenotypical and functional characteristics as do SCs from adult 46,XY patients?<\/jats:p>\n <\/jats:sec>\n \n SUMMARY ANSWER<\/jats:title>\n Isolated SCs from patients with Klinefelter syndrome (KS) can be expanded in vitro while maintaining their characteristics and a stable karyotype, similar to SCs from 46,XY patients.<\/jats:p>\n <\/jats:sec>\n \n WHAT IS KNOWN ALREADY<\/jats:title>\n The mechanism leading to testicular tissue degeneration in KS is still unknown. A few recent studies highlight the main role played by SCs in the physiopathology of the disease, but new study models based on co-culture or testicular organoids are needed to further understand the SC\u2019s involvement in the mechanism of testicular degeneration and fibrosis, and to find therapeutical targets. KS SC expansion could be the first step towards developing such in vitro study models. SCs have been isolated from 46,XY men and expanded in vitro while maintaining the expression of phenotypical and functional markers, but propagation of SCs from KS men has not been achieved yet.<\/jats:p>\n <\/jats:sec>\n \n STUDY DESIGN, SIZE, DURATION<\/jats:title>\n Testicular tissue was obtained during a testicular sperm extraction procedure for infertility treatment between 2019 and 2021 from three azoospermic adult KS (47,XXY) men (33\u00b13.6\u2009years old) and from three control patients (46,XY) (36\u00b12\u2009years old) presenting with obstructive azoospermia. SCs isolated from frozen-thawed tissue of KS and 46,XY patients were cultured for 60\u2009days and compared. All patients signed an informed consent according to the ethical board approval of the study protocol.<\/jats:p>\n <\/jats:sec>\n \n PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n Testicular biopsies obtained from KS (n\u2009=\u20093) and 46,XY (n\u2009=\u20093) adult patients were slow-frozen. After tissue thawing SCs were isolated using a double-step enzymatic digestion and differential plating, and cultured for 60\u2009days in DMEM medium containing FBS. Analyses were performed at different culture times (passages 5 (P5) and 10 (P10)). Quantification of cells using immunofluorescence (IF) for cell type-specific markers (Sox9, GATA4, ACTA2, INSL3, MAGEA4), SCs characterization using both IF and quantitative real-time PCR for GDNF, BMP4, AR and CLDN11 and cells karyotyping were performed.<\/jats:p>\n <\/jats:sec>\n \n MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n We demonstrate for the first time that a small population of human SCs isolated from frozen-thawed testis of adult KS patients can be expanded in vitro while retaining expression of characteristic markers of SCs and the 47,XXY karyotype, and exhibiting cell-specific functional proteins and gene expression (GDNF, BMP4, AR, and CLDN11) after 60\u2009days in culture. At P10, 83.39\u2009\u00b1\u20094.2% of cultured cells from KS men and 85.34\u2009\u00b1\u20094.1% from 46,XY men expressed Sox9, and 88.8\u2009\u00b1\u20093.9% of KS cells versus 82.9\u2009\u00b1\u20093.2% of the control cells were positive for GATA4 without any differences between two groups; both Sox9 and GATA4 are typical SC markers. No differences were found between KS and 46,XY SCs in vitro in terms of cells expansion (exponential growth between P1 and P10 with an average cell count of 2.8\u00b11.5\u00d7107 versus 3.8\u00b11.2\u00d7107 respectively for the KS and control groups at P10). There was no significant statistical difference for functional proteins and genes expressions (GDNF, BMP4, AR, and CLDN11) neither between KS SCs and control SCs nor between P5 and P10.<\/jats:p>\n <\/jats:sec>\n \n LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n The small number of donor samples is a limitation but it is due to limited availability of tissue for research in KS populations. Although no differences were observed in SCs function in the culture of isolated SCs after 60\u2009days, the possibility of a SCs dysfunction needs to be investigated in more complex 3-dimensional models allowing the establishment of a proper cell organization and further analyses of cell functions and interactions during longer culture periods.<\/jats:p>\n <\/jats:sec>\n \n WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n The demonstration of the possibility to propagate KS SCs in vitro could be useful to build new in vitro models for deciphering testicular cell interactions, determining deficient signalling pathways involved in impaired spermatogenesis, and identifying targets for infertility treatment in KS. As the cell numbers achieved in this study are higher than cell numbers used to develop testicular organoids, we may expect to be able to understand the behaviour and physiopathology of SCs in the disease during the long-term culture of these organoids. Such models could be further applied to understand other causes of deficiencies in seminiferous tubules.<\/jats:p>\n <\/jats:sec>\n \n STUDY FUNDING\/COMPETING INTEREST(S)<\/jats:title>\n M.G.G is funded by a grant from the Cliniques Universitaires Saint-Luc (FRC) for the research project on Klinefelter Syndrome Physiopathology. The authors declare no conflicts of interest.<\/jats:p>\n <\/jats:sec>\n \n TRIAL REGISTRATION NUMBER<\/jats:title>\n NCT05997706.<\/jats:p>\n <\/jats:sec>","DOI":"10.1093\/humrep\/deae201","type":"journal-article","created":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T01:38:29Z","timestamp":1725586709000},"page":"2400-2410","source":"Crossref","is-referenced-by-count":2,"title":["Long-term culture of human Sertoli cells from adult Klinefelter patients as a first step to develop new tools for unravelling the testicular physiopathology"],"prefix":"10.1093","volume":"39","author":[{"given":"Maria Grazia","family":"Giudice","sequence":"first","affiliation":[{"name":"P\u00f4le de recherche en Physiologie de la Reproduction (REPR), Institut de Recherche Exp\u00e9rimentale et Clinique (IREC), Universit\u00e9 Catholique de Louvain , Brussels,","place":["Belgium"]},{"name":"Department of Gynecology-Andrology, Cliniques Universitaires Saint-Luc , 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Current understanding of its structure and physiology","volume":"11","author":"Luaces","year":"2023","journal-title":"Front Cell Dev Biol"},{"key":"2024110408200734200_deae201-B35","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1093\/humrep\/det068","article-title":"Sertoli cells from non-obstructive azoospermia and obstructive azoospermia patients show distinct morphology, Raman spectrum and biochemical phenotype","volume":"28","author":"Ma","year":"2013","journal-title":"Hum Reprod"},{"key":"2024110408200734200_deae201-B36","doi-asserted-by":"crossref","first-page":"1924","DOI":"10.1016\/j.ajhg.2021.09.001","article-title":"Comparative single-cell analysis of biopsies clarifies pathogenic mechanisms in Klinefelter syndrome","volume":"108","author":"Mahyari","year":"2021","journal-title":"Am J Hum Genet"},{"key":"2024110408200734200_deae201-B37","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":"2024110408200734200_deae201-B38","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1095\/biolreprod.105.047365","article-title":"Glial cell-line derived neurotrophic factor-mediated RET signaling regulates spermatogonial stem cell fate","volume":"74","author":"Naughton","year":"2006","journal-title":"Biol Reprod"},{"key":"2024110408200734200_deae201-B39","first-page":"1","article-title":"Evaluation of apoptosis-related genes and hormone secretion profiles using three dimensional culture system of human testicular organoids","volume":"12","author":"Nikmahzar","year":"2023","journal-title":"Galen Med J"},{"key":"2024110408200734200_deae201-B41","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1530\/REP-08-0363","article-title":"Intracellular pH regulation in human Sertoli cells: role of membrane 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tissues","volume":"550","author":"Tukiainen","year":"2017","journal-title":"Nature"},{"key":"2024110408200734200_deae201-B51","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1016\/j.fertnstert.2020.01.018","article-title":"Characterization of the stem cell niche components within the seminiferous tubules in testicular biopsies of Klinefelter patients","volume":"113","author":"Van Saen","year":"2020","journal-title":"Fertil Steril"},{"key":"2024110408200734200_deae201-B52","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1111\/j.1651-2227.2010.02112.x","article-title":"Expression of selected genes escaping from X inactivation in the 41, XX(Y) mouse model for Klinefelter\u2019s syndrome","volume":"100","author":"Werler","year":"2011","journal-title":"Acta Paediatr"},{"key":"2024110408200734200_deae201-B53","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1093\/humrep\/dep338","article-title":"KIT ligand and bone morphogenetic protein signaling enhances human 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