title: Infertility with defective spermatogenesis and hypotestosteronemia in male mice lacking the androgen receptor in Sertoli cells.
abstract: Androgens and the androgen receptor (AR) play important roles in male fertility, although the detailed mechanisms, particularly how androgen/AR influences spermatogenesis in particular cell types, remain unclear. Using a Cre-Lox conditional knockout strategy, we generated a tissue-specific knockout mouse with the AR gene deleted only in Sertoli cells (S-AR(-/y)). Phenotype analyses show the S-AR(-/y) mice were indistinguishable from WT AR mice (B6 AR(+/y)) with the exception of testes, which were significantly atrophied. S-AR(-/y) mice were infertile, with spermatogenic arrest predominately at the diplotene premeiotic stage and almost no sperm detected in the epididymides. S-AR(-/y) mice also have lower serum testosterone concentrations and higher serum leuteinizing hormone concentrations than B6 AR(+/y) mice. Further mechanistic studies demonstrated that S-AR(-/y) mice have defects in the expression of anti-Müllerian hormone, androgen-binding protein, cyclin A1, and sperm-1, which play important roles in the control of spermatogenesis and/or steroidogenesis. Together, our Sertoli cell-specific AR knockout mice provide in vivo evidence of the need for functional AR in Sertoli cells to maintain normal spermatogenesis and testosterone production, and ensure normal male fertility.
authors.affiliation: George Whipple Laboratory for Cancer Research, Departments of Pathology and Urology, and The Cancer Center, University of Rochester, Rochester, NY 14642, USA. chang@urmc.rochester.edu
authors.forename: Chawnshang
authors.initials: C
authors.lastname: Chang
authors.forename: Yen-Ta
authors.initials: YT
authors.lastname: Chen
authors.forename: Shauh-Der
authors.initials: SD
authors.lastname: Yeh
authors.forename: Qingquan
authors.initials: Q
authors.lastname: Xu
authors.forename: Ruey-Sheng
authors.initials: RS
authors.lastname: Wang
authors.forename: Florian
authors.initials: F
authors.lastname: Guillou
authors.forename: Henry
authors.initials: H
authors.lastname: Lardy
authors.forename: Shuyuan
authors.initials: S
authors.lastname: Yeh
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D007248:Infertility, Male / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009845:Oligospermia / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000172:deficiency* / Q000235:genetics; D012708:Sertoli Cells / Q000378:metabolism*; D013091:Spermatogenesis / Q000502:physiology*; D013093:Spermatogonia / Q000502:physiology; D013737:Testis / Q000378:metabolism; D013739:Testosterone / Q000097:blood / Q000172:deficiency*
chemical_list: D011944:Receptors, Androgen; D013739:Testosterone