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This version published online on September 14, 2006
Endocrinology, doi:10.1210/en.2006-0138
A more recent version of this article appeared on December 1, 2006
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Submitted on February 3, 2006
Accepted on August 24, 2006

Androgen Receptor in Sertoli Cell Is Essential For Germ Cell Nursery and Junctional Complex Formation in Mouse Testes

Ruey-Sheng Wang, Shuyuan Yeh, Lu-Min Chen, Hung-Yun Lin, Caixia Zhang, Jing Ni, Cheng-Chia Wu, P. Anthony di Sant'Agnese, Karen L. de Mesy-Bentley, Chii-Ruey Tzeng, and Chawnshang Chang*

George H. Whipple Lab for Cancer Research, Departments of Urology and Pathology, University of Rochester, Rochester, NY 14642; Graduate Institute of Medical Sciences and Department of Obstetrics and Gynecology, Taipei Medical University, Taipei 110, Taiwan; Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung, Taiwan

* To whom correspondence should be addressed. E-mail: chang{at}urmc.rochester.edu.

To examine the role of androgen receptor (AR) in Sertoli cells (SC), we applied Sertoli cell-specific androgen receptor knock-out (S-AR-/y) mouse to further evaluate the chronological changes of seminiferous tubules and the molecular mechanisms of SC androgen/AR signals on spermatogenesis. Testes morphology began changing as early as PD 10.5 in wild-type (wt), but not in S-AR-/y mice. After puberty (PD 50), the SC nuclei of wt testes migrated to the basal area of the seminiferous epithelium; however, in S-AR-/y testes, SC nuclei were disarranged and dislocated. Results from electron microscopy further showed an obvious duplication of basal lamina of the seminiferous epithelium in S-AR-/y testes at PD 50 compared with wt testes. Using quantitative RT-PCR analyses, the expression of SC gene profiles were compared in PD 10.5 testes. In S-AR-/y testes, the expression levels of 1) vimentin was significantly increased and laminin {alpha}5 was significantly decreased in PD 10.5, which contributed to functional defects in cytoskeletons and production of basement membrane component of SC leading to cell morphology deterioration and thus affecting the integrity of seminiferous epithelium; 2) claudin-11, occludin, and gelsolin were significantly decreased in PD 10.5, which contributed to defects in intact junctional complex formation of SC leading to impairment of the integrity of the blood-testis barrier; 3) Cacna1a, tPA, transferrin, and eFABP were significantly decreased in PD 10.5, which contributed to functional defects in production and/or secretion of specific proteases, transport proteins, and paracrine factors of SC leading to impairment of its germ cells nursery functions.
Key words: Androgen receptor • Sertoli cell • Sertoli cell-specific AR knockout




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