Infertility with defective spermatogenesis and hypotestosteronemia in male mice lacking the androgen receptor in Sertoli cells

Chawnshang Chang, Yen T. Chen, Shauh D. Yeh, Qingquan Xu, Ruey Sheng Wang, Florian Guillou, Henry Lardy, Shuyuan Yeh

Research output: Contribution to journalArticle

323 Citations (Scopus)

Abstract

Androgens and the androgen receptor (AR) play important roles in male fertility, although the detailed mechanisms, particularly how androgen/AR influences spermatogenesis in particular cell types, remain unclear. Using a Cre-Lox conditional knockout strategy, we generated a tissue-specific knockout mouse with the AR gene deleted only in Sertoli cells (S-AR-/y). Phenotype analyses show the S-AR-/y mice were indistinguishable from WT AR mice (B6 AR+/y) with the exception of testes, which were significantly atrophied. S-AR-/v mice were infertile, with spermatogenic arrest predominately at the diplotene premeiotic stage and almost no sperm detected in the epididymides. S-AR-/y mice also have lower serum testosterone concentrations and higher serum leuteinizing hormone concentrations than B6 AR+/y mice. Further mechanistic studies demonstrated that S-AR-/y mice have defects in the expression of anti-Müllerian hormone, androgen-binding protein, cyclin A1, and sperm-1, which play important roles in the control of spermatogenesis and/or steroidogenesis. Together, our Sertoli cell-specific AR knockout mice provide in vivo evidence of the need for functional AR in Sertoli cells to maintain normal spermatogenesis and testosterone production, and ensure normal male fertility.

Original languageEnglish
Pages (from-to)6876-6881
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number18
DOIs
Publication statusPublished - May 4 2004

Keywords

  • Anti-Müllerian hormone
  • Knockout mice
  • Testosterone

ASJC Scopus subject areas

  • General
  • Genetics

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