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Androgen Receptor in Sertoli Cells Is Not Required for Testosterone-Induced Suppression of Spermatogenesis, but Contributes to Sertoli Cell Organization in Utp14b^jsd Mice

KAREL DE GENDT

ROBERT E. BRAUN^,

GUIDO VERHOEVEN

From the ^* Department of Experimental Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas; the Laboratory for Experimental Medicine and Endocrinology, Catholic University of Leuven, Leuven, Belgium; and the Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington.
Present address: The Jackson Laboratory, Bar Harbor, ME.

Correspondence to: Gensheng Wang, Department of Experimental Radiation Oncology, Unit 66, M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030 (e-mail: genwang{at}mdanderson.org).

Testosterone acting through the androgen receptor (AR) maintains the arrest of spermatogonial differentiation in juvenile spermatogonial depletion (jsd mutation in the Utp14b gene) mutant adult male mice. It is not known which of the somatic cell types expressing AR mediates this inhibition. To determine whether Sertoli cells are responsible, we selectively eliminated AR in Sertoli cells in jsd mice containing a floxed-Ar gene and an anti-Müllerian hormone–Cre transgene. In these Sertoli AR-knockout (SCARKO)-jsd mice, spermatogonial differentiation did not recover. However, the normal organization of Sertoli cell nuclei was drastically disrupted in SCARKO-jsd mice compared with SCARKO or jsd mice. In addition, the extent of ectoplasmic specializations was reduced; tight junctions were not found; vinculin, an anchoring protein found in ectoplasmic specializations, became uniformly distributed in the cytoplasm; and the adult Sertoli cells showed excess heterochromatin subjacent to their nuclear envelope. Despite the abnormalities in Sertoli cells in SCARKO-jsd mice, global suppression of testosterone action and levels was still effective in restoring the differentiated germ cells, and this was accompanied by an improved arrangement of Sertoli cell nuclei. We conclude that Sertoli cells are not targets for the testosterone-mediated inhibition of spermatogonial differentiation in jsd mice, and that both AR in Sertoli cells and the presence of differentiated germ cells contribute to maintaining the organization of Sertoli cells within the seminiferous tubules.

     Key words: Testis, spermatogonial differentiation, juvenile spermatogonial depletion, azoospermia, vinculin

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