TY - JOUR
T1 - Oligozoospermia with normal fertility in male mice lacking the androgen receptor in testis peritubular myoid cells
AU - Zhang, Caixia
AU - Yeh, Shuyuan
AU - Chen, Yen Ta
AU - Wu, Cheng Chia
AU - Chuang, Kuang Hsiang
AU - Lin, Hung Yun
AU - Wang, Ruey Sheng
AU - Chang, Yu Jia
AU - Mendis-Handagama, Chamindrani
AU - Hu, Liquan
AU - Lardy, Henry
AU - Chang, Chawnshang
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/11/21
Y1 - 2006/11/21
N2 - Androgens and the androgen receptor (AR) play important roles in the testes. Previously we have shown that male total AR knockout (T-AR -/y) mice revealed incomplete germ cell development and lowered serum testosterone levels, which resulted in azoospermia and infertility. However, the consequences of AR loss in particular types of testicular cells remain unclear. Using a Cre-loxP conditional knockout strategy, we generated a tissue-selective knockout mouse with the AR gene deleted in testis peritubular myoid cells (PM-AR-/y). Phenotype analyses showed that PM-AR -/y mice were indistinguishable from WT AR (AR+/y) mice with the exception of smaller testes size. PM-AR-/y mice have serum testosterone concentrations comparable with AR+/y mice. PM-AR -/y mice have oligozoospermia in the epididymis; however, fertility was normal. Although normal germ cell distribution ratio was found, total germ cell number decreased in PM-AR-/y mice. Further mechanistic studies demonstrated that PM-AR-/y mice have defects in the expression of Sertoli cells' functional marker genes such as tranferrin, epidermal fatty acid-binding protein, androgen-binding protein, and other junction genes including occludin, testin, nectin, zyxin, vinculin, lamininγ3, gelsolin, connection43, and N-cadherin. Furthermore, there were defects in peritubular myoid cell contractility-related genes such as endothelin-1, endothelin receptor A and B, adrenomedullin, adrenomedullin receptor, and vasopressin receptor 1a. Together, our PM-AR-/y mice provide in vivo evidence for the requirement of functional AR in peritubular myoid cells to maintain normal Sertoli cells function and peritubular myoid cell contractility, thus ensuring normal spermatogenesis and sperm output.
AB - Androgens and the androgen receptor (AR) play important roles in the testes. Previously we have shown that male total AR knockout (T-AR -/y) mice revealed incomplete germ cell development and lowered serum testosterone levels, which resulted in azoospermia and infertility. However, the consequences of AR loss in particular types of testicular cells remain unclear. Using a Cre-loxP conditional knockout strategy, we generated a tissue-selective knockout mouse with the AR gene deleted in testis peritubular myoid cells (PM-AR-/y). Phenotype analyses showed that PM-AR -/y mice were indistinguishable from WT AR (AR+/y) mice with the exception of smaller testes size. PM-AR-/y mice have serum testosterone concentrations comparable with AR+/y mice. PM-AR -/y mice have oligozoospermia in the epididymis; however, fertility was normal. Although normal germ cell distribution ratio was found, total germ cell number decreased in PM-AR-/y mice. Further mechanistic studies demonstrated that PM-AR-/y mice have defects in the expression of Sertoli cells' functional marker genes such as tranferrin, epidermal fatty acid-binding protein, androgen-binding protein, and other junction genes including occludin, testin, nectin, zyxin, vinculin, lamininγ3, gelsolin, connection43, and N-cadherin. Furthermore, there were defects in peritubular myoid cell contractility-related genes such as endothelin-1, endothelin receptor A and B, adrenomedullin, adrenomedullin receptor, and vasopressin receptor 1a. Together, our PM-AR-/y mice provide in vivo evidence for the requirement of functional AR in peritubular myoid cells to maintain normal Sertoli cells function and peritubular myoid cell contractility, thus ensuring normal spermatogenesis and sperm output.
KW - Knockout
KW - Spermatogenesis
KW - Transgelin
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U2 - 10.1073/pnas.0608556103
DO - 10.1073/pnas.0608556103
M3 - Article
C2 - 17095600
AN - SCOPUS:33845221110
SN - 0027-8424
VL - 103
SP - 17718
EP - 17723
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 47
ER -