Regulation of meiotic progression by Sertoli-cell androgen signaling

We combine synchronization of spermatogenesis, cytological analyses and single-cell RNA-seq (scRNA-seq) 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, whereas scRNA-seq analysis 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. Overall design: Single-cell RNA-seq (scRNA-seq) analysis on whole testes in the Sertoli cell androgen receptor knockout (SCARKO) mutant and control mice at eight, thirteen and sixteen days past spermatogenesis synchronization and twenty-one days post-partum unsynchronized whole testes.