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Loss of PBX1 function in Leydig cells causes testicular dysgenesis and male sterility.
Wang, Fei-Chen; Zhang, Xiao-Na; Wu, Shi-Xin; He, Zhen; Zhang, Lu-Yao; Yang, Qi-En.
Afiliación
  • Wang FC; Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, 810001, Qinghai, China.
  • Zhang XN; University of Chinese Academy of Sciences, Beijing, 100049, China.
  • Wu SX; Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, 810001, Qinghai, China.
  • He Z; University of Chinese Academy of Sciences, Beijing, 100049, China.
  • Zhang LY; Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, 810001, Qinghai, China.
  • Yang QE; University of Chinese Academy of Sciences, Beijing, 100049, China.
Cell Mol Life Sci ; 81(1): 212, 2024 May 09.
Article en En | MEDLINE | ID: mdl-38724675
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Testículo / Testosterona / Factor de Transcripción 1 de la Leucemia de Células Pre-B / Infertilidad Masculina / Células Intersticiales del Testículo Límite: Animals Idioma: En Revista: Cell Mol Life Sci Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Testículo / Testosterona / Factor de Transcripción 1 de la Leucemia de Células Pre-B / Infertilidad Masculina / Células Intersticiales del Testículo Límite: Animals Idioma: En Revista: Cell Mol Life Sci Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza