PT  - JOURNAL ARTICLE
AU  - Hailey Larose
AU  - Travis Kent
AU  - Qianyi Ma
AU  - Adrienne Niederriter Shami
AU  - Nadia Harerimana
AU  - Jun Z. Li
AU  - Saher Sue Hammoud
AU  - Mary Ann Handel
TI  - Regulation of meiotic progression by Sertoli-cell androgen signaling
AID  - 10.1101/2020.05.26.117093
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.05.26.117093
4099  - http://biorxiv.org/content/early/2020/05/31/2020.05.26.117093.short
4100  - http://biorxiv.org/content/early/2020/05/31/2020.05.26.117093.full
AB  - 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 regulates specific meiosis 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.Competing Interest StatementThe authors have declared no competing interest.