PDF(Pubmed)
Abstract：
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 Pbx1 in Leydig cells caused spermatogenic defects and complete sterility. Histological examinations revealed that Pbx1 deletion impaired testicular structure and led to disorganization of the seminiferous tubules. Single-cell RNA-seq analysis revealed that loss of Pbx1 function affected the fate decisions of progenitor Leydig cells and altered the transcription of genes associated with testosterone synthesis in the adult testis. Pbx1 directly regulates the transcription of genes that play important roles in steroidogenesis (Prlr, Nr2f2 and Nedd4). Further analysis demonstrated that deletion of Pbx1 leads to a significant decrease in testosterone levels, accompanied by increases in pregnenolone, androstenedione and luteinizing 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.
摘要：
睾丸间质细胞是睾丸间质组织的重要组成部分，是男性雄激素的主要来源。Leydig细胞的功能缺陷通常会导致严重的生殖障碍；然而，这些细胞的命运决定和类固醇生成背后的转录程序尚未完全定义。在这项研究中,我们报道，同源结构域转录因子PBX1是小鼠Leydig细胞分化和睾酮产生的主要调节因子。PBX1在成年睾丸间质细胞和肾小管周围肌样细胞中高表达。Leydig细胞中Pbx1的条件缺失导致生精缺陷和完全不育。组织学检查显示，Pbx1缺失损害了睾丸结构，并导致生精小管解体。单细胞RNA-seq分析显示，Pbx1功能的丧失影响了祖细胞Leydig细胞的命运决定，并改变了成年睾丸中与睾丸激素合成相关的基因的转录。Pbx1直接调节在类固醇生成中起重要作用的基因的转录(Prlr，Nr2f2和Nedd4）。进一步的分析表明，Pbx1的缺失导致睾酮水平显着降低，伴随着孕烯醇酮的增加，雄烯二酮和促黄体激素。总的来说，我们的数据显示，PBX1对于维持Leydig细胞功能是必不可少的。这些发现提供了有关睾丸发育不全和睾丸间质细胞激素分泌调节的见解。
