Androgen receptor (AR) signaling in Sertoli cells is known to be important for germ-cell progression through meiosis, but the extent to which androgens indirectly regulate specific meiotic stages is not known. Here, we combine synchronization of spermatogenesis, cytological analyses and single-cell RNAseq (scRNAseq) in the Sertoli cell androgen receptor knockout (SCARKO) mutant and control mice, and demonstrate that SCARKO mutant spermatocytes exhibited normal expression and localization of key protein markers of meiotic prophase events, indicating that initiation of meiotic prophase is not androgen dependent. However, spermatocytes from SCARKO testes failed to acquire competence for the meiotic division phase. ScRNAseq analysis of wild type and SCARKO mutant testes revealed a molecular transcriptomic block in an early meiotic prophase state (leptotene/zygotene) in mutant germ cells, and identified several misregulated genes in SCARKO Sertoli cells, many of which have been previously implicated in male infertility. Together, our coordinated cytological and single-cell RNAseq analyses identified germ-cell intrinsic and extrinsic genes responsive to Sertoli-cell androgen signaling that promotes cellular states permissive for the meiotic division phase.

已知支持细胞中的雄激素受体（AR）信号对于通过减数分裂的生殖细胞进程很重要，但是雄激素间接调节特定减数分裂阶段的程度尚不清楚。在这里，我们在结合精子发生，细胞学分析和单细胞RNA测序（scRNAseq）的同步小号ertoli Ç ELL一个ndrogen ř eceptor ķ诺克öut（SCARKO）突变小鼠和对照小鼠，并证明SCARKO突变精子细胞表现出减数分裂前期事件的关键蛋白标志物的正常表达和定位，表明减数分裂前期的启动不依赖雄激素。然而，来自SCARKO睾丸的精母细胞未能获得减数分裂分裂阶段的能力。对野生型和SCARKO突变型睾丸的ScRNAseq分析揭示了突变生殖细胞中处于减数分裂前期阶段早期状态的分子转录组阻滞（瘦素/合子），并在SCARKO Sertoli细胞中鉴定了几个失调的基因，其中许多以前与男性不育有关。 。一起，