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Infertility with defective spermatogenesis and steroidogenesis in male mice lacking androgen receptor in Leydig cells

Qingquan Xu1, Hung-Yun Lin, Shauh-Der Yeh

  • 1Department of Pathology, the Cancer Center, University of Rochester, 601 Elmwood Ave, Box 626, Rochester, NY 14642, USA.

Endocrine
|October 24, 2007
PubMed

Insights

Functional androgen receptor (AR) in Leydig cells is crucial for male fertility. Loss of AR in Leydig cells impairs sperm production and lowers testosterone, causing infertility in mice.

Area of Science:

  • Reproductive Biology
  • Endocrinology
  • Molecular Genetics

Background:

  • Androgen receptor (AR) plays a vital role in male fertility.
  • Previous studies showed AR knockout mice have impaired germ cell development and infertility.
  • The specific role of AR in Leydig cells regarding male fertility remained unclear.

Purpose of the Study:

  • To investigate the consequences of androgen receptor (AR) loss specifically in Leydig cells.
  • To determine the necessity of functional AR in Leydig cells for spermatogenesis and testosterone production.

Main Methods:

  • Generated a conditional knockout mouse model (L-AR(-/y)) with AR deleted in Leydig cells using a Cre-LoxP system driven by the Amhr2 promoter.
  • Conducted phenotype analyses, including reproductive organ assessment, sperm count, and serum hormone level measurements.
  • Performed mechanistic studies to identify alterations in steroidogenic enzymes.

Main Results:

  • L-AR(-/y) mice exhibited atrophied testes and epididymis, leading to infertility.
  • Spermatogenesis was arrested at the round spermatid stage with absence of epididymal sperm.
  • Hypotestosteronemia in L-AR(-/y) mice was linked to altered expression of key steroidogenic enzymes (17beta-HSD3, 3beta-HSD6, P450c17), not reduced Leydig cell numbers.

Conclusions:

  • Functional androgen receptor (AR) in Leydig cells is essential for maintaining normal spermatogenesis.
  • AR in Leydig cells is critical for regulating testosterone production through steroidogenic enzyme activity.
  • These findings highlight the indispensable role of Leydig cell AR in male fertility.

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