Oligozoospermia with normal fertility in male mice lacking the androgen receptor in testis peritubular myoid cells

Caixia Zhang, Shuyuan Yeh, Yen Ta Chen, Cheng Chia Wu, Kuang Hsiang Chuang, Hung Yun Lin, Ruey Sheng Wang, Yu Jia Chang, Chamindrani Mendis-Handagama, Liquan Hu, Henry Lardy, Chawnshang Chang

研究成果: 雜誌貢獻文章

94 引文 (Scopus)

摘要

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.

原文英語
頁(從 - 到)17718-17723
頁數6
期刊Proceedings of the National Academy of Sciences of the United States of America
103
發行號47
DOIs
出版狀態已發佈 - 十一月 21 2006
對外發佈Yes

指紋

Oligospermia
Fertility
Testis
Androgen Receptors
Germ Cells
Sertoli Cells
Genes
Testosterone
Zyxin
Adrenomedullin Receptors
Androgen-Binding Protein
mouse AR protein
Gelsolin
Occludin
Vinculin
Adrenomedullin
Endothelin A Receptors
Vasopressin Receptors
Fatty Acid-Binding Proteins
Endothelin Receptors

ASJC Scopus subject areas

  • Genetics
  • General

引用此文

Oligozoospermia with normal fertility in male mice lacking the androgen receptor in testis peritubular myoid cells. / Zhang, Caixia; Yeh, Shuyuan; Chen, Yen Ta; Wu, Cheng Chia; Chuang, Kuang Hsiang; Lin, Hung Yun; Wang, Ruey Sheng; Chang, Yu Jia; Mendis-Handagama, Chamindrani; Hu, Liquan; Lardy, Henry; Chang, Chawnshang.

於: Proceedings of the National Academy of Sciences of the United States of America, 卷 103, 編號 47, 21.11.2006, p. 17718-17723.

研究成果: 雜誌貢獻文章

Zhang, C, Yeh, S, Chen, YT, Wu, CC, Chuang, KH, Lin, HY, Wang, RS, Chang, YJ, Mendis-Handagama, C, Hu, L, Lardy, H & Chang, C 2006, 'Oligozoospermia with normal fertility in male mice lacking the androgen receptor in testis peritubular myoid cells', Proceedings of the National Academy of Sciences of the United States of America, 卷 103, 編號 47, 頁 17718-17723. https://doi.org/10.1073/pnas.0608556103
Zhang, Caixia ; Yeh, Shuyuan ; Chen, Yen Ta ; Wu, Cheng Chia ; Chuang, Kuang Hsiang ; Lin, Hung Yun ; Wang, Ruey Sheng ; Chang, Yu Jia ; Mendis-Handagama, Chamindrani ; Hu, Liquan ; Lardy, Henry ; Chang, Chawnshang. / Oligozoospermia with normal fertility in male mice lacking the androgen receptor in testis peritubular myoid cells. 於: Proceedings of the National Academy of Sciences of the United States of America. 2006 ; 卷 103, 編號 47. 頁 17718-17723.
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abstract = "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.",
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AU - Chuang, Kuang Hsiang

AU - Lin, Hung Yun

AU - Wang, Ruey Sheng

AU - Chang, Yu Jia

AU - Mendis-Handagama, Chamindrani

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