Transcriptional profiling of the hormone-responsive stages of spermatogenesis reveals cell-, stage-, and hormone-specific events.
Spermatogenesis occurs within the highly complex seminiferous epithelium. This cyclic process is accompanied by dynamic stage-specific transcriptional changes and is driven by androgens and FSH by mechanisms that are unclear. Here we report the impact of acute androgen and FSH suppression on the transcriptional dynamics of the seminiferous epithelium. We used transcriptional profiling to compare the most hormone-sensitive seminiferous epithelial stages (VII and VIII) from control and hormone-suppressed adult rats, together with publicly available datasets to delineate stage- and cell-specific transcriptional changes. The analyses reveal that, in these stages, there was a hormone-responsive down-regulation of spermatogonial and Sertoli cell transcripts maximally expressed in the earlier spermatogenic stages (I-VI). Transcripts expressed in Sertoli cells from stage VII and beyond were both up- and down-regulated by hormone suppression, with lysosome function, immune system-related genes, and lipid metabolism predicted to be hormone responsive. Hormone-responsive genes with putative roles in integrin-mediated cell adhesion were also identified. In pachytene spermatocytes, there was an initiation of transcription likely important for the completion of meiosis. A transcriptional switch in round spermatids was observed, from a hormone-responsive down-regulation of transcripts expressed in steps 1-7 spermatids to a hormone-independent up-regulation of transcripts expressed in steps 8-11 and likely involved in spermatid differentiation and DNA compaction. This study points to the existence of hormone-responsive global transcriptional repressors in Sertoli cells, spermatogonia, and spermatids and reveals novel and diverse cell-specific responses of the seminiferous epithelium to hormone suppression.
Prince Henry's Institute of Medical Research, PO Box 5152, Clayton, VIC 3168, Australia. liza.odonnell@princehenrys.org
Liza
L
O'Donnell
Kyriakos
K
Pratis
Andrea
A
Wagenfeld
Ulrich
U
Gottwald
Jörg
J
Müller
Gabriele
G
Leder
Robert I
RI
McLachlan
Peter G
PG
Stanton
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D002454:Cell Differentiation; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012708:Sertoli Cells / Q000187:drug effects / Q000378:metabolism; D013045:Species Specificity; D013091:Spermatogenesis / Q000187:drug effects*; D013093:Spermatogonia / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*
D000728:Androgens; D005640:Follicle Stimulating Hormone