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Title: A Sertoli cell-selective knockout of the androgen receptor causes spermatogenic arrest in meiosis
Authors: De Gendt, Karel ×
Swinnen, Johan
Saunders, Philippa T K
Schoonjans, Luc
Dewerchin, Mieke
Devos, Ann
Tan, Karen
Atanassova, Nina
Claessens, Frank
Lécureuil, Charlotte
Heyns, Walter
Carmeliet, Peter
Guillou, Florian
Sharpe, Richard M
Verhoeven, Guido #
Issue Date: Feb-2004
Publisher: National Academy of Sciences
Series Title: Proceedings of the National Academy of Sciences of the United States of America vol:101 issue:5 pages:1327-32
Abstract: Androgens control spermatogenesis, but germ cells themselves do not express a functional androgen receptor (AR). Androgen regulation is thought to be mediated by Sertoli and peritubular myoid cells, but their relative roles and the mechanisms involved remain largely unknown. Using Cre/loxP technology, we have generated mice with a ubiquitous knockout of the AR as well as mice with a selective AR knockout in Sertoli cells (SC) only. Mice with a floxed exon 2 of the AR gene were crossed with mice expressing Cre recombinase ubiquitously or selectively in SC (under control of the anti-Müllerian hormone gene promoter). AR knockout males displayed a complete androgen insensitivity phenotype. Testes were located abdominally, and germ cell development was severely disrupted. In contrast, SC AR knockout males showed normal testis descent and development of the male urogenital tract. Expression of the homeobox gene Pem, which is androgen-regulated in SC, was severely decreased. Testis weight was reduced to 28% of that in WT littermates. Stereological analysis indicated that the number of SC was unchanged, whereas numbers of spermatocytes, round spermatids, and elongated spermatids were reduced to 64%, 3%, and 0% respectively of WT. These changes were associated with increased germ cell apoptosis and grossly reduced expression of genes specific for late spermatocyte or spermatid development. It is concluded that cell-autonomous action of the AR in SC is an absolute requirement for androgen maintenance of complete spermatogenesis, and that spermatocyte/spermatid development/survival critically depends on androgens.
ISSN: 0027-8424
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical and Experimental Endocrinology
Biochemistry Section (Medicine) (-)
Molecular and Vascular Biology
Laboratory of Molecular Endocrinology
Laboratory of Lipid Metabolism and Cancer (+)
Laboratory of Angiogenesis and Vascular Metabolism (VIB-KU Leuven Centre for Cancer Biology) (+)
× corresponding author
# (joint) last author

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