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

Qingquan Xu, Hung Yun Lin, Shauh Der Yeh, I. Chen Yu, Ruey Shen Wang, Yen Ta Chen, Caixia Zhang, Saleh Altuwaijri, Lu Min Chen, Kuang Hsiang Chuang, Han-Sun Chiang, Shuyuan Yeh, Chawnshang Chang

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

Androgen and the androgen receptor (AR) have been shown to play critical roles in male fertility. Our previous data demonstrated that mice lacking AR (AR-/y) revealed incomplete germ cell development and lowered serum testosterone levels, which resulted in azoospermia and infertility. However, the consequences of AR loss in Leydig cells remain largely unknown. Using a Cre-LoxP conditional knockout strategy, we generated a tissue-specific knockout mouse (L-AR-/y) with the AR gene deleted by the anti-Müllerian hormone receptor-2 (Amhr2) promoter driven Cre expressed in Leydig cells. Phenotype analyses show that the outside appearance of L-AR-/y mice was indistinguishable from wild type mice (AR+/y), but with atrophied testes and epididymis. L-AR-/y mice were infertile, with spermatogenic arrest predominately at the round spermatid stage and no sperm could be detected in the epididymis. L-AR-/y mice also have lower serum testosterone concentrations and higher serum leuteinizing hormone and follicle-stimulating hormone concentrations than AR+/y mice. Further mechanistic studies demonstrated that hypotestosteronemia in L-AR-/y mice is not caused by reducing numbers of Leydig cells, but instead by the alterations of several key steroidogenic enzymes, including 17β-HSD3, 3β-HSD6, and P450c17. Together, L-AR-/y mice provide in vivo evidence that functional AR in Leydig cells is essential to maintain normal spermatogenesis, testosterone production, and required for normal male fertility.

Original languageEnglish
Pages (from-to)96-106
Number of pages11
JournalEndocrine
Volume32
Issue number1
DOIs
Publication statusPublished - Aug 2007

Keywords

  • Androgen receptor
  • Leydig cell
  • Spermatogenesis
  • Steroidogenesis

ASJC Scopus subject areas

  • Endocrinology

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