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Endocrinology, doi:10.1210/en.2009-0755
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Endocrinology Vol. 150, No. 11 5074-5084
Copyright © 2009 by The Endocrine Society

Transcriptional Profiling of the Hormone-Responsive Stages of Spermatogenesis Reveals Cell-, Stage-, and Hormone-Specific Events

Liza O'Donnell, Kyriakos Pratis, Andrea Wagenfeld, Ulrich Gottwald, Jörg Müller, Gabriele Leder, Robert I. McLachlan and Peter G. Stanton

Prince Henry’s Institute of Medical Research (L.O., K.P., R.I.M., P.G.S.), Clayton, Victoria, 3168 Australia; and Global Therapeutic Research (A.W., U.G., J.M., G.L.), Bayer Schering Pharma AG, 13353 Berlin, Germany

Address all correspondence and requests for reprints to: Dr Liza O’Donnell, Prince Henry’s Institute of Medical Research, PO Box 5152, Clayton, VIC 3168, Australia. E-mail: liza.odonnell{at}princehenrys.org.

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.







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Copyright © 2009 by The Endocrine Society