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Mol. Life Sci."],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Leydig cells are essential components of testicular interstitial tissue and serve as a primary source of androgen in males. A functional deficiency in Leydig cells often causes severe reproductive disorders; however, the transcriptional programs underlying the fate decisions and steroidogenesis of these cells have not been fully defined. In this study, we report that the homeodomain transcription factor PBX1 is a master regulator of Leydig cell differentiation and testosterone production in mice. PBX1 was highly expressed in Leydig cells and peritubular myoid cells in the adult testis. Conditional deletion of <jats:italic>Pbx1<\/jats:italic> in Leydig cells caused spermatogenic defects and complete sterility. Histological examinations revealed that <jats:italic>Pbx1<\/jats:italic> deletion impaired testicular structure and led to disorganization of the seminiferous tubules. Single-cell RNA-seq analysis revealed that loss of <jats:italic>Pbx1<\/jats:italic> function affected the fate decisions of progenitor Leydig cells and altered the transcription of genes associated with testosterone synthesis in the adult testis. <jats:italic>Pbx1<\/jats:italic> directly regulates the transcription of genes that play important roles in steroidogenesis (<jats:italic>Prlr<\/jats:italic>, <jats:italic>Nr2f2<\/jats:italic> and <jats:italic>Nedd4<\/jats:italic>). Further analysis demonstrated that deletion of <jats:italic>Pbx1<\/jats:italic> leads to a significant decrease in testosterone levels, accompanied by increases in pregnenolone, androstenedione and\u00a0luteinizing hormone. Collectively, our data revealed that PBX1 is indispensable for maintaining Leydig cell function. These findings provide insights into testicular dysgenesis and the regulation of hormone secretion in Leydig cells.<\/jats:p>\n                <jats:p><jats:bold>Graphical abstract<\/jats:bold><\/jats:p>","DOI":"10.1007\/s00018-024-05249-5","type":"journal-article","created":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T16:01:47Z","timestamp":1715270507000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Loss of PBX1 function in Leydig cells causes testicular dysgenesis and male sterility"],"prefix":"10.1007","volume":"81","author":[{"given":"Fei-Chen","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Na","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-Xin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu-Yao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9849-6996","authenticated-orcid":false,"given":"Qi-En","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,9]]},"reference":[{"key":"5249_CR1","doi-asserted-by":"publisher","first-page":"2756","DOI":"10.12688\/f1000research.9375.1","volume":"5","author":"JM Bieniek","year":"2016","unstructured":"Bieniek JM, Lo KC (2016) Recent advances in understanding & managing male infertility. 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