Open AccessRegulation of meiotic progression by Sertoli-cell androgen signaling
Author(s) -
Hailey Larose,
Travis Kent,
Qianyi Ma,
Adrienne Niederriter Shami,
Nadia V. Harerimana,
Jun Z. Li,
Saher Sue Hammoud,
Mary Ann Handel
Publication year - 2020
Publication title -
molecular biology of the cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.463
H-Index - 225
eISSN - 1939-4586
pISSN - 1059-1524
DOI - 10.1091/mbc.e20-05-0334
Subject(s) - sertoli cell , biology , meiosis , androgen receptor , microbiology and biotechnology , androgen , signal transduction , spermatogenesis , endocrinology , genetics , gene , hormone , prostate cancer , cancer
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 S ertoli- c ell a ndrogen r eceptor k nock o ut (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 scRNAseq analyses identified germ-cell intrinsic and extrinsic genes responsive to Sertoli-cell androgen signaling that promotes cellular states permissive for the meiotic division phase.