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Infertility with defective spermatogenesis and steroidogenesis in male mice lacking androgen receptor in Leydig cells
- Source :
- Endocrine; August 2007, Vol. 32 Issue: 1 p96-106, 11p
- Publication Year :
- 2007
-
Abstract
- Abstracts: 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<superscript>−/y</superscript>) 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<superscript>−/y</superscript>) 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<superscript>−/y</superscript> mice was indistinguishable from wild type mice (AR<superscript>+/y</superscript>), but with atrophied testes and epididymis. L-AR<superscript>−/y</superscript> mice were infertile, with spermatogenic arrest predominately at the round spermatid stage and no sperm could be detected in the epididymis. L-AR<superscript>−/y</superscript> mice also have lower serum testosterone concentrations and higher serum leuteinizing hormone and follicle-stimulating hormone concentrations than AR<superscript>+/y</superscript> mice. Further mechanistic studies demonstrated that hypotestosteronemia in L-AR<superscript>−/y</superscript> 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<superscript>−/y</superscript> 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.
Details
- Language :
- English
- ISSN :
- 1355008x and 15590100
- Volume :
- 32
- Issue :
- 1
- Database :
- Supplemental Index
- Journal :
- Endocrine
- Publication Type :
- Periodical
- Accession number :
- ejs12797527
- Full Text :
- https://doi.org/10.1007/s12020-007-9015-0