{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T04:41:49Z","timestamp":1792384909827,"version":"4.4.0"},"reference-count":70,"publisher":"The Endocrine Society","issue":"11","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":10,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN-2022-03933"],"award-info":[{"award-number":["RGPIN-2022-03933"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-186209"],"award-info":[{"award-number":["PJT-186209"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004888","name":"Fondation du CHU de Qu\u00e9bec-Universit\u00e9 Laval","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004888","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Differentiated Leydig cells (LCs) produce testosterone and INSL3, 2 hormones essential for male sex differentiation and fertility. In mice, the developmental origin of adult Leydig cells (ALCs) and the presence of stem Leydig cells (SLCs) in adulthood remain unresolved. To investigate this, we used the Leydig cell-specific Insl3iCre line combined with Rosa26lox-STOP-lox-iDTR\/lox-STOP-lox-TdTomato to genetically ablate the committed LC lineage in adult mice. These mice displayed a normal phenotype without diphtheria toxin (DT). Following DT administration, TdTomato-positive and CYP17A1-positive LCs were eliminated within 4 to 7 days, leading to marked reductions in testosterone levels and androgen-dependent organ weights. Activated Caspase 3 confirmed apoptosis of targeted Leydig cells during the acute ablation phase. This was accompanied by transient macrophage recruitment as shown by F4-80 immunofluorescence, consistent with their involvement in clearing apoptotic Leydig cells. Importantly, COUP-TFII-positive\/\u03b1SMA-negative\/CYP17A1-negative\/TdTomato-negative cells persisted adjacent to peritubular and perivascular myoid cells, identifying a candidate Insl3-negative precursor population. Newly emerging TdTomato-positive cells subsequently appeared predominantly around seminiferous tubules and, to a lesser extent, blood vessels, marking the onset of Leydig cell regeneration. Testosterone levels progressively recovered as these cells acquired CYP17A1 expression and populated the interstitial compartment. By 65 days post-DT, the ALC population and endocrine function were fully restored. These findings provide strong functional evidence for adult SLCs capable of repopulating the LC lineage after complete ablation and identify the peritubular compartment as a major regenerative niche. This inducible LC-depletion mouse model provides a powerful tool to investigate SLC biology and the mechanisms governing LC differentiation and testicular endocrine homeostasis.<\/jats:p>","DOI":"10.1210\/endocr\/bqag113","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T11:49:10Z","timestamp":1791460150000},"source":"Crossref","is-referenced-by-count":0,"title":["Genetic ablation of the adult Leydig cell lineage reveals stem Leydig cells and a peritubular regenerative niche in mice"],"prefix":"10.1210","volume":"167","author":[{"given":"Laurie","family":"Boudreau","sequence":"first","affiliation":[{"name":"Reproduction, Mother and Child Health, Centre de recherche du centre hospitalier universitaire de Qu\u00e9bec\u2014Universit\u00e9 Laval , Qu\u00e9bec City, QC G1V 4G2 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas M","family":"Robert","sequence":"additional","affiliation":[{"name":"Reproduction, Mother and Child Health, Centre de recherche du centre hospitalier universitaire de Qu\u00e9bec\u2014Universit\u00e9 Laval , Qu\u00e9bec City, QC G1V 4G2 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4738-6284","authenticated-orcid":false,"given":"Jacques J","family":"Tremblay","sequence":"additional","affiliation":[{"name":"Reproduction, Mother and Child Health, Centre de recherche du centre hospitalier universitaire de Qu\u00e9bec\u2014Universit\u00e9 Laval , Qu\u00e9bec City, QC G1V 4G2 ,","place":["Canada"]},{"name":"Department of Obstetrics, Gynecology, and Reproduction, Faculty of Medicine, Centre de recherche en Reproduction, D\u00e9veloppement et Sant\u00e9 Interg\u00e9n\u00e9rationnelle, Universit\u00e9 Laval , Qu\u00e9bec City, QC G1V 0A6 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"issue":"1","key":"2026101900264761500_bqag113-B1","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1093\/biolre\/ioy059","article-title":"Leydig cells: formation, function, and regulation","volume":"99","author":"Zirkin","year":"2018","journal-title":"Biol Reprod"},{"key":"2026101900264761500_bqag113-B2","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2022.1086276","article-title":"Emerging concepts on Leydig cell development in fetal and adult testis","volume":"13","author":"Bhattacharya","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"1","key":"2026101900264761500_bqag113-B3","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1530\/JOE-20-0168","article-title":"Diverse functions of insulin-like 3 peptide","volume":"247","author":"Esteban-Lopez","year":"2020","journal-title":"J Endocrinol"},{"issue":"3","key":"2026101900264761500_bqag113-B4","doi-asserted-by":"crossref","DOI":"10.1002\/mrd.23739","article-title":"Fetal Leydig cells: what we know and what we don\u2019t","volume":"91","author":"Jiang","year":"2024","journal-title":"Mol Reprod Dev"},{"key":"2026101900264761500_bqag113-B5","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.semcdb.2016.03.003","article-title":"Development, function and fate of fetal Leydig cells","volume":"59","author":"Wen","year":"2016","journal-title":"Semin Cell Dev Biol"},{"issue":"12","key":"2026101900264761500_bqag113-B6","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2025.116674","article-title":"Tracing the origin of testosterone-producing Leydig cells during pubertal development, homeostasis, and regeneration","volume":"44","author":"Yu","year":"2025","journal-title":"Cell Rep"},{"issue":"4","key":"2026101900264761500_bqag113-B7","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1002\/rmb2.12287","article-title":"Development of fetal and adult Leydig cells","volume":"18","author":"Shima","year":"2019","journal-title":"Reprod Med Biol"},{"issue":"11","key":"2026101900264761500_bqag113-B8","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2022.110935","article-title":"Deciphering the origins and fates of steroidogenic lineages in the mouse testis","volume":"39","author":"Ademi","year":"2022","journal-title":"Cell Rep"},{"issue":"2","key":"2026101900264761500_bqag113-B9","doi-asserted-by":"crossref","DOI":"10.1210\/endocr\/bqaf012","article-title":"A new Leydig cell-exclusive Cre line allows lineage tracing of fetal and adult Leydig cell populations in the mouse","volume":"166","author":"Robert","year":"2025","journal-title":"Endocrinology"},{"issue":"1","key":"2026101900264761500_bqag113-B10","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1530\/REP-09-0349","article-title":"Androgen profiles during pubertal Leydig cell development in mice","volume":"140","author":"Wu","year":"2010","journal-title":"Reproduction"},{"key":"2026101900264761500_bqag113-B11","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/bs.ctdb.2026.03.002","article-title":"Current understanding of adult stem cells in Leydig cell biology","volume":"168","author":"Wang","year":"2026","journal-title":"Curr Top Dev Biol"},{"key":"2026101900264761500_bqag113-B12","doi-asserted-by":"crossref","DOI":"10.3389\/fphys.2017.00430","article-title":"Insights into the development of the adult Leydig cell lineage from stem Leydig cells","volume":"8","author":"Ye","year":"2017","journal-title":"Front Physiol"},{"issue":"4","key":"2026101900264761500_bqag113-B13","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1002\/bdrc.20192","article-title":"Stem Leydig cells: from fetal to aged animals","volume":"90","author":"Chen","year":"2010","journal-title":"Birth Defects Res C Embryo Today"},{"issue":"2","key":"2026101900264761500_bqag113-B14","doi-asserted-by":"crossref","first-page":"105","DOI":"10.3109\/01485018908986831","article-title":"Turnover time of Leydig cells and other interstitial cells in testes of adult rats","volume":"23","author":"Teerds","year":"1989","journal-title":"Arch Androl"},{"key":"2026101900264761500_bqag113-B15","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/bs.vh.2020.12.023","article-title":"Leydig cell aging: molecular mechanisms and treatments","volume":"115","author":"Papadopoulos","year":"2021","journal-title":"Vitam Horm"},{"issue":"3","key":"2026101900264761500_bqag113-B16","doi-asserted-by":"crossref","first-page":"201","DOI":"10.3109\/13685538.2015.1052392","article-title":"Age-related testosterone decline is due to waning of both testicular and hypothalamic-pituitary function","volume":"18","author":"Golan","year":"2015","journal-title":"Aging Male"},{"key":"2026101900264761500_bqag113-B17","doi-asserted-by":"crossref","DOI":"10.1016\/j.mce.2019.110449","article-title":"Characterization and differentiation of CD51(+) stem Leydig cells in adult mouse testes","volume":"493","author":"Chen","year":"2019","journal-title":"Mol Cell Endocrinol"},{"issue":"1","key":"2026101900264761500_bqag113-B18","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S0300-483X(97)03626-3","article-title":"Thymic regression and apoptosis in the rat after treatment with the Leydig cell cytotoxin ethylene dimethanesulphonate (EDS)","volume":"120","author":"Morris","year":"1997","journal-title":"Toxicology"},{"issue":"6","key":"2026101900264761500_bqag113-B19","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1006\/phrs.1997.0186","article-title":"Effects of ethane dimethanesulfonate on the structure of adult male rat adrenal cortex","volume":"35","author":"Plecas","year":"1997","journal-title":"Pharmacol Res"},{"issue":"5","key":"2026101900264761500_bqag113-B20","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1002\/j.1939-4640.1992.tb03334.x","article-title":"Direct effects of ethane dimethanesulphonate on epididymal function in adult rats. An in vitro demonstration","volume":"13","author":"Klinefelter","year":"1992","journal-title":"J Androl"},{"issue":"2","key":"2026101900264761500_bqag113-B21","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0232-1513(11)80008-3","article-title":"Changes in the rat lymphoid tissues after Leydig cell destruction by ethane-1,2-dimethanesulphonate","volume":"41","author":"Leeming","year":"1991","journal-title":"Exp Pathol"},{"issue":"2","key":"2026101900264761500_bqag113-B22","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/0041-008X(90)90189-2","article-title":"Multiple effects of ethane dimethanesulfonate on the epididymis of adult rats","volume":"105","author":"Klinefelter","year":"1990","journal-title":"Toxicol Appl Pharmacol"},{"issue":"4","key":"2026101900264761500_bqag113-B23","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1002\/j.1939-4640.1990.tb00155.x","article-title":"Does ethane 1,2-dimethanesulphonate (EDS) have a direct cytotoxic effect on the seminiferous epithelium of the rat testis?","volume":"11","author":"Sprando","year":"1990","journal-title":"J Androl"},{"issue":"1","key":"2026101900264761500_bqag113-B24","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/BF02940288","article-title":"Testicular endocrine effects of alkane methanesulphonates related to the Leydig cell cytotoxic compound, EDS","volume":"26","author":"Edwards","year":"1990","journal-title":"Cancer Chemother Pharmacol"},{"issue":"3","key":"2026101900264761500_bqag113-B25","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1210\/endo-126-3-1618","article-title":"Ethylene dimethanesulfonate inhibits the function of Sertoli cells in culture at sublethal doses","volume":"126","author":"Roberts","year":"1990","journal-title":"Endocrinology"},{"issue":"1","key":"2026101900264761500_bqag113-B26","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/0303-7207(88)90094-9","article-title":"In vitro effects of ethylene-dimethane sulfonate (EDS) on Leydig cells: inhibition of steroid production and cytotoxic effects are dependent on species and age of rat","volume":"55","author":"Rommerts","year":"1988","journal-title":"Mol Cell Endocrinol"},{"issue":"1","key":"2026101900264761500_bqag113-B27","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1677\/joe.0.1170011","article-title":"Characterization of the regenerated Leydig cell population of the rat after destruction by ethylene-1,2-dimethanesulphonate","volume":"117","author":"Edwards","year":"1988","journal-title":"J Endocrinol"},{"issue":"2","key":"2026101900264761500_bqag113-B28","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1677\/joe.0.1260229","article-title":"Development of a new Leydig cell population after the destruction of existing Leydig cells by ethane dimethane sulphonate in rats: an autoradiographic study","volume":"126","author":"Teerds","year":"1990","journal-title":"J Endocrinol"},{"issue":"2","key":"2026101900264761500_bqag113-B29","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1210\/endo-118-2-709","article-title":"Ethylene dimethanesulfonate destroys Leydig cells in the rat testis","volume":"118","author":"Morris","year":"1986","journal-title":"Endocrinology"},{"issue":"1","key":"2026101900264761500_bqag113-B30","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/BF00225571","article-title":"Selective destruction and regeneration of rat Leydig cells in vivo. A new method for the study of seminiferous tubular-interstitial tissue interaction","volume":"242","author":"Kerr","year":"1985","journal-title":"Cell Tissue Res"},{"issue":"5","key":"2026101900264761500_bqag113-B31","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1095\/biolreprod33.5.1213","article-title":"Specific destruction of Leydig cells in mature rats after in vivo administration of ethane dimethyl sulfonate","volume":"33","author":"Molenaar","year":"1985","journal-title":"Biol Reprod"},{"issue":"2","key":"2026101900264761500_bqag113-B32","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0041-008X(91)90023-8","article-title":"Immature rat Leydig cells are intrinsically less sensitive than adult Leydig cells to ethane dimethanesulfonate","volume":"111","author":"Kelce","year":"1991","journal-title":"Toxicol Appl Pharmacol"},{"issue":"2","key":"2026101900264761500_bqag113-B33","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/0303-7207(85)90097-8","article-title":"Ethane dimethane sulphonate (EDS) specifically inhibits LH stimulated steroidogenesis in Leydig cells isolated from mature rats but not in cells from immature rats","volume":"42","author":"Rommerts","year":"1985","journal-title":"Mol Cell Endocrinol"},{"issue":"2","key":"2026101900264761500_bqag113-B34","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1007\/BF00215530","article-title":"Ultrastructural analysis of the effect of ethane dimethanesulphonate on the testis of the rat, guinea pig, hamster and mouse","volume":"249","author":"Kerr","year":"1987","journal-title":"Cell Tissue Res"},{"issue":"1","key":"2026101900264761500_bqag113-B35","doi-asserted-by":"crossref","first-page":"3876","DOI":"10.1038\/s41467-021-24130-8","article-title":"TCF21(+) mesenchymal cells contribute to testis somatic cell development, homeostasis, and regeneration in mice","volume":"12","author":"Shen","year":"2021","journal-title":"Nat Commun"},{"issue":"2","key":"2026101900264761500_bqag113-B36","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.bbadis.2011.11.013","article-title":"Up-regulation of NDRG2 through nuclear factor-kappa B is required for Leydig cell apoptosis in both human and murine infertile testes","volume":"1822","author":"Li","year":"2012","journal-title":"Biochim Biophys Acta"},{"issue":"1","key":"2026101900264761500_bqag113-B37","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/nn.2467","article-title":"A robust and high-throughput Cre reporting and characterization system for the whole mouse brain","volume":"13","author":"Madisen","year":"2010","journal-title":"Nat Neurosci"},{"issue":"6","key":"2026101900264761500_bqag113-B38","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1038\/nmeth762","article-title":"A Cre-inducible diphtheria toxin receptor mediates cell lineage ablation after toxin administration","volume":"2","author":"Buch","year":"2005","journal-title":"Nat Methods"},{"issue":"3","key":"2026101900264761500_bqag113-B39","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1111\/andr.12601","article-title":"Phosphorylation of GATA4 serine 105 but not serine 261 is required for testosterone production in the male mouse","volume":"7","author":"Bergeron","year":"2019","journal-title":"Andrology"},{"issue":"1","key":"2026101900264761500_bqag113-B40","doi-asserted-by":"crossref","first-page":"18332","DOI":"10.1038\/s41598-021-97729-y","article-title":"VCAM1-alpha4beta1 integrin interaction mediates interstitial tissue reconstruction in 3-D re-aggregate culture of dissociated prepubertal mouse testicular cells","volume":"11","author":"Abe","year":"2021","journal-title":"Sci Rep"},{"key":"2026101900264761500_bqag113-B41","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2022.894437","article-title":"Immune cells as critical regulators of steroidogenesis in the testis and beyond","volume":"13","author":"Gu","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"2","key":"2026101900264761500_bqag113-B42","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1006\/taap.1995.1030","article-title":"Hamster Leydig cells are less sensitive to ethane dimethanesulfonate when compared to rat Leydig cells both in vivo and in vitro","volume":"130","author":"Gray","year":"1995","journal-title":"Toxicol Appl Pharmacol"},{"issue":"5","key":"2026101900264761500_bqag113-B43","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1095\/biolreprod50.5.1151","article-title":"Effects of ethane dimethanesulfonate (EDS) on adult and immature rabbit Leydig cells: comparison with EDS-treated rat Leydig cells","volume":"50","author":"Laskey","year":"1994","journal-title":"Biol Reprod"},{"issue":"3","key":"2026101900264761500_bqag113-B44","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/0016-6480(90)90063-R","article-title":"Morphological and hormonal changes in the frog, Rana esculenta, testis after administration of ethane dimethane sulfonate","volume":"79","author":"Minucci","year":"1990","journal-title":"Gen Comp Endocrinol"},{"issue":"4","key":"2026101900264761500_bqag113-B45","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1095\/biolreprod40.4.801","article-title":"Differential effects of the destruction of Leydig cells by administration of ethane dimethane sulphonate to postnatal rats","volume":"40","author":"Risbridger","year":"1989","journal-title":"Biol Reprod"},{"issue":"2","key":"2026101900264761500_bqag113-B46","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1530\/REP-10-0404","article-title":"Good planning and serendipity: exploiting the Cre\/Lox system in the testis","volume":"141","author":"Smith","year":"2011","journal-title":"Reproduction"},{"key":"2026101900264761500_bqag113-B47","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.semcdb.2021.05.007","article-title":"Stem Leydig cells: current research and future prospects of regenerative medicine of male reproductive health","volume":"121","author":"Li","year":"2022","journal-title":"Semin Cell Dev Biol"},{"issue":"1","key":"2026101900264761500_bqag113-B48","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1210\/endrev\/bnz013","article-title":"Stem Leydig cells in the adult testis: characterization, regulation and potential applications","volume":"41","author":"Chen","year":"2020","journal-title":"Endocr Rev"},{"issue":"6","key":"2026101900264761500_bqag113-B49","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1095\/biolreprod60.6.1437","article-title":"Identification of markers for precursor and Leydig cell differentiation in the adult rat testis following ethane dimethyl sulphonate administration","volume":"60","author":"Teerds","year":"1999","journal-title":"Biol Reprod"},{"issue":"4","key":"2026101900264761500_bqag113-B50","first-page":"209","article-title":"Degeneration and restoration of spermatogenesis in relation to the changes in Leydig cell population following ethane dimethanesulfonate treatment in adult rats","volume":"35","author":"Bakalska","year":"2001","journal-title":"Endocr Regul"},{"issue":"Suppl 1","key":"2026101900264761500_bqag113-B51","first-page":"535","article-title":"Morphological studies on the origin of adult-type Leydig cells in rat testis","volume":"100","author":"Haider","year":"1995","journal-title":"Ital J Anat Embryol"},{"issue":"5","key":"2026101900264761500_bqag113-B52","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1083\/jcb.200409107","article-title":"Progenitor cells of the testosterone-producing Leydig cells revealed","volume":"167","author":"Davidoff","year":"2004","journal-title":"J Cell Biol"},{"issue":"8","key":"2026101900264761500_bqag113-B53","doi-asserted-by":"crossref","first-page":"2719","DOI":"10.1073\/pnas.0507692103","article-title":"In search of rat stem Leydig cells: identification, isolation, and lineage-specific development","volume":"103","author":"Ge","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"10","key":"2026101900264761500_bqag113-B54","doi-asserted-by":"crossref","first-page":"5002","DOI":"10.1210\/en.2012-1417","article-title":"Identification, proliferation, and differentiation of adult Leydig stem cells","volume":"153","author":"Stanley","year":"2012","journal-title":"Endocrinology"},{"issue":"10","key":"2026101900264761500_bqag113-B55","doi-asserted-by":"crossref","first-page":"2666","DOI":"10.1073\/pnas.1519395113","article-title":"Regulation of seminiferous tubule-associated stem Leydig cells in adult rat testes","volume":"113","author":"Li","year":"2016","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"2026101900264761500_bqag113-B56","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.stem.2019.12.005","article-title":"The dynamic transcriptional cell atlas of testis development during human puberty","volume":"26","author":"Guo","year":"2020","journal-title":"Cell Stem Cell"},{"key":"2026101900264761500_bqag113-B57","doi-asserted-by":"crossref","DOI":"10.1016\/j.mce.2021.111179","article-title":"Differentiation of seminiferous tubule-associated stem cells into Leydig cell and myoid cell lineages","volume":"525","author":"Zhao","year":"2021","journal-title":"Mol Cell Endocrinol"},{"key":"2026101900264761500_bqag113-B58","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.100396","article-title":"A single-cell atlas of the testicular interstitium defines Leydig progenitor networks sustaining Leydig cell homeostasis across the lifespan","volume":"14","author":"Huang","year":"2025","journal-title":"Elife"},{"issue":"5","key":"2026101900264761500_bqag113-B59","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1083\/jcb.149.5.1019","article-title":"Leydig cell loss and spermatogenic arrest in platelet-derived growth factor (PDGF)\u2014a-deficient mice","volume":"149","author":"Gnessi","year":"2000","journal-title":"J Cell Biol"},{"issue":"23","key":"2026101900264761500_bqag113-B60","doi-asserted-by":"crossref","first-page":"3255","DOI":"10.1101\/gad.1723908","article-title":"The PDGF signaling pathway controls multiple steroid-producing lineages","volume":"22","author":"Schmahl","year":"2008","journal-title":"Genes Dev"},{"issue":"6","key":"2026101900264761500_bqag113-B61","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1095\/biolreprod.114.117473","article-title":"Regulation of the proliferation and differentiation of Leydig stem cells in the adult testis","volume":"90","author":"Odeh","year":"2014","journal-title":"Biol Reprod"},{"issue":"22","key":"2026101900264761500_bqag113-B62","doi-asserted-by":"crossref","first-page":"3745","DOI":"10.1242\/dev.024786","article-title":"Notch signaling maintains Leydig progenitor cells in the mouse testis","volume":"135","author":"Tang","year":"2008","journal-title":"Development"},{"issue":"1","key":"2026101900264761500_bqag113-B63","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1006\/excr.1993.1249","article-title":"DNA fragmentation and cytolysis in U937 cells treated with diphtheria toxin or other inhibitors of protein synthesis","volume":"208","author":"Kochi","year":"1993","journal-title":"Exp Cell Res"},{"key":"2026101900264761500_bqag113-B64","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/bs.ctdb.2026.04.004","article-title":"Role of macrophages in testis function","volume":"169","author":"Matsuyama","year":"2026","journal-title":"Curr Top Dev Biol"},{"issue":"2","key":"2026101900264761500_bqag113-B65","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1530\/jrf.0.1020393","article-title":"Requirement for testicular macrophages in Leydig cell proliferation and differentiation during prepubertal development in rats","volume":"102","author":"Gaytan","year":"1994","journal-title":"J Reprod Fertil"},{"issue":"6","key":"2026101900264761500_bqag113-B66","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1002\/j.1939-4640.1994.tb00499.x","article-title":"Effects of macrophage depletion at different times after treatment with ethylene dimethane sulfonate (EDS) on the regeneration of Leydig cells in the adult rat","volume":"15","author":"Gaytan","year":"1994","journal-title":"J Androl"},{"issue":"1","key":"2026101900264761500_bqag113-B67","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1530\/jrf.0.1010175","article-title":"Selective depletion of testicular macrophages and prevention of Leydig cell repopulation after treatment with ethylene dimethane sulfonate in rats","volume":"101","author":"Gaytan","year":"1994","journal-title":"J Reprod Fertil"},{"issue":"5","key":"2026101900264761500_bqag113-B68","doi-asserted-by":"crossref","DOI":"10.3390\/biom11050697","article-title":"Macrophages and stem cells\u2014two to tango for tissue repair?","volume":"11","author":"Manole","year":"2021","journal-title":"Biomolecules"},{"key":"2026101900264761500_bqag113-B69","doi-asserted-by":"crossref","DOI":"10.7717\/peerj.14053","article-title":"Macrophages play a key role in tissue repair and regeneration","volume":"10","author":"Yu","year":"2022","journal-title":"PeerJ"},{"issue":"3","key":"2026101900264761500_bqag113-B70","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.immuni.2016.02.015","article-title":"Macrophages in tissue repair, regeneration, and fibrosis","volume":"44","author":"Wynn","year":"2016","journal-title":"Immunity"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/endo\/advance-article-pdf\/doi\/10.1210\/endocr\/bqag113\/71722946\/bqag113.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/endo\/article-pdf\/167\/11\/bqag113\/71722946\/bqag113.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/endo\/article-pdf\/167\/11\/bqag113\/71722946\/bqag113.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T04:27:01Z","timestamp":1792384021000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/doi\/10.1210\/endocr\/bqag113\/8886359"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,29]]},"references-count":70,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2026,9,29]]}},"URL":"https:\/\/doi.org\/10.1210\/endocr\/bqag113","relation":{},"ISSN":["1945-7170"],"issn-type":[{"value":"1945-7170","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,11]]},"published":{"date-parts":[[2026,9,29]]},"article-number":"bqag113"}}