Androgen receptor in sertoli cell is essential for germ cell nursery and junctional complex formation in mouse testes.
To examine the role of androgen receptor (AR) in Sertoli cells (SC), we used a SC-specific AR knockout (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 postnatal day (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 were significantly increased and laminin alpha5 was significantly decreased in PD 10.5, which contributed to functional defects in cytoskeletons and production of the 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) calcium channel, voltage-dependent, P/Q-type, alpha1A subunit; tissue-type plasminogen activator; transferrin; and epidermal fatty-acid-binding protein 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.
Wang
Ruey-Sheng
RS
George H. Whipple Lab for Cancer Research, Department of Urology, University of Rochester, Rochester, New York 14642, USA, and Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung, Taiwan.
Yeh
Shuyuan
S
Chen
Lu-Min
LM
Lin
Hung-Yun
HY
Zhang
Caixia
C
Ni
Jing
J
Wu
Cheng-Chia
CC
di Sant'Agnese
P Anthony
PA
deMesy-Bentley
Karen L
KL
Tzeng
Chii-Ruey
CR
Chang
Chawnshang
C
D000818:Animals; D001485:Basement Membrane / Q000002:abnormalities; D002467:Cell Nucleus / Q000648:ultrastructure; D057167:Claudins; D005260:Female; D018260:Gelsolin / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells / Q000502:physiology*; D007365:Intercellular Junctions / Q000648:ultrastructure*; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D007797:Laminin / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D062793:Occludin; D012333:RNA, Messenger / Q000378:metabolism; D011944:Receptors, Androgen / Q000502:physiology*; D012708:Sertoli Cells / Q000378:metabolism*; D013737:Testis / Q000166:cytology / Q000254:growth & development* / Q000648:ultrastructure*; D014746:Vimentin / Q000378:metabolism
D057167:Claudins; C492354:Cldn11 protein, mouse; D018260:Gelsolin; D036341:Intercellular Signaling Peptides and Proteins; D007797:Laminin; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D062793:Occludin; C568986:Ocln protein, mouse; D012333:RNA, Messenger; D011944:Receptors, Androgen; D014746:Vimentin; C097043:laminin alpha5