PUBLICATION

Expression profiling identifies Sertoli and Leydig cell genes as Fsh targets in adult zebrafish testis

Authors
Crespo, D., Assis, L.H., Furmanek, T., Bogerd, J., Schulz, R.W.
ID
ZDB-PUB-160828-3
Date
2016
Source
Molecular and Cellular Endocrinology   437: 237-251 (Journal)
Registered Authors
Bogerd, Jan, Schulz, RĂ¼diger W.
Keywords
Follicle-stimulating hormone, RNA sequencing, Spermatogenesis, Zebrafish
Datasets
GEO:GSE84436
MeSH Terms
  • Aging/genetics
  • Androgens/metabolism
  • Animals
  • Cell Proliferation/genetics
  • Follicle Stimulating Hormone/pharmacology*
  • Gene Expression Profiling*
  • Gene Expression Regulation, Developmental/drug effects*
  • HEK293 Cells
  • Humans
  • Leydig Cells/cytology
  • Leydig Cells/drug effects
  • Leydig Cells/metabolism*
  • Male
  • Protein Interaction Maps
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Recombinant Proteins/pharmacology
  • Sertoli Cells/cytology
  • Sertoli Cells/drug effects
  • Sertoli Cells/metabolism*
  • Signal Transduction/drug effects
  • Spermatogenesis/drug effects
  • Spermatogenesis/genetics
  • Spermatogonia/cytology
  • Spermatogonia/drug effects
  • Spermatogonia/metabolism
  • Testis/drug effects
  • Testis/metabolism*
  • Transcriptome/genetics
  • Zebrafish/genetics*
  • Zebrafish/growth & development*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
27566230 Full text @ Mol. Cell. Endocrinol.
Abstract
Spermatogonial stem cells are quiescent, undergo self-renewal or differentiating divisions, thereby forming the cellular basis of spermatogenesis. This cellular development is orchestrated by follicle-stimulating hormone (FSH), through the production of Sertoli cell-derived factors, and by Leydig cell-released androgens. Here, we investigate the transcriptional events induced by Fsh in a steroid-independent manner on the restart of zebrafish (Danio rerio) spermatogenesis ex vivo, using testis from adult males where type A spermatogonia were enriched by estrogen treatment in vivo. Under these conditions, RNA sequencing preferentially detected differentially expressed genes in somatic/Sertoli cells. Fsh-stimulated spermatogonial proliferation was accompanied by modulating several signaling systems (i.e. Tgf-β, Hedgehog, Wnt and Notch pathways). In silico protein-protein interaction analysis indicated a role for Hedgehog family members potentially integrating signals from different pathways during fish spermatogenesis. Moreover, Fsh had a marked impact on metabolic genes, such as lactate and fatty acid metabolism, or on Sertoli cell barrier components. Fish Leydig cells express the Fsh receptor and one of the most robust Fsh-responsive genes was insulin-like 3 (insl3), a Leydig cell-derived growth factor. Follow-up work showed that recombinant zebrafish Insl3 mediated pro-differentiation effects of Fsh on spermatogonia in an androgen-independent manner. Our experimental approach allowed focusing on testicular somatic genes in zebrafish and showed that the activity of signaling systems known to be relevant in stem cell systems was modulated by Fsh, providing promising leads for future work, as exemplified by the studies on Insl3.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping