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Androgens and spermatogenesis: lessons from transgenic mouse models.

Guido Verhoeven1, Ariane Willems, Evi Denolet

  • 1Department of Experimental Medicine, Laboratory for Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium. guido.verhoeven@med.kuleuven.be

Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
|April 21, 2010
PubMed
Summary

Transgenic mouse models reveal that the androgen receptor (AR) in Sertoli cells is crucial for spermatogenesis. Identifying androgen-regulated genes aids in understanding male fertility and potential therapeutic targets.

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Area of Science:

  • Reproductive Biology
  • Molecular Endocrinology
  • Genetics

Background:

  • Androgens are vital for spermatogenesis, but their precise cellular and molecular control mechanisms are complex.
  • Transgenic mouse models offer powerful tools to dissect these mechanisms.
  • The androgen receptor (AR) is a key mediator of androgen action.

Purpose of the Study:

  • To elucidate the role of the androgen receptor (AR) in Sertoli cells (SC) and other testicular cells in regulating spermatogenesis.
  • To identify androgen-regulated genes involved in spermatogenesis using transcriptional profiling.
  • To explore the potential of identified genes as diagnostic tools or therapeutic targets.

Main Methods:

  • Cell-selective ablation of the androgen receptor (AR) in mouse Sertoli cells (SC).
  • Generation and analysis of mouse models with diminished AR expression or altered CAG repeat length.
  • Transcriptional profiling of mouse models with various AR knockouts to identify androgen-regulated genes.

Main Results:

  • Ablation of AR in SC completely blocks meiosis, confirming SC as the primary mediator of androgen effects in spermatogenesis.
  • Mutations affecting AR expression or CAG repeat length mimic human fertility disorders without impacting sexual development.
  • Transcriptional profiling identified numerous candidate androgen-regulated genes, with limited overlap between different knockout models, including genes related to tubular restructuring, cell junctions, cytoskeleton, solute transport, and vitamin A metabolism.

Conclusions:

  • Sertoli cells are the principal cellular mediators of androgen action in spermatogenesis.
  • Identified androgen-regulated genes provide insights into male fertility regulation.
  • Further research is needed to validate the physiological relevance of these genes and their potential as diagnostic or therapeutic targets for modulating spermatogenesis.