Differential effects of spermatogenesis and fertility in mice lacking androgen receptor in individual testis cells

Meng Yin Tsai, Shauh Der Yeh, Ruey Sheng Wang, Shuyuan Yeh, Caixia Zhang, Hung Yun Lin, Chii Ruey Tzeng, Chawnshang Chang

Research output: Contribution to journalArticle

129 Citations (Scopus)

Abstract

Using a Cre-Lox conditional knockout strategy, we generated a germ cell-specific androgen receptor (AR) knockout mouse (GAR-/y) with normal spermatogenesis. Sperm count and motility in epididymis from AR -/y mice are similar to that of WT (G-AR+/y) mice. Furthermore, fertility tests show there was no difference in fertility, and almost 100% of female pups sired by G-AR-/y males younger than 15 weeks carried the deleted AR allele, suggesting the efficient AR knockout occurred in germ cells during meiosis. Together, these data provide in vivo evidence showing male mice without AR in germ cells can still have normal spermatogenesis and fertility, suggesting the essential roles of AR during spermatogenesis might come from indirect cell- cell communication in a paracrine fashion. We then compared the consequences of AR loss in the spermatogenesis and fertility of G-AR-/y mice with two other testicular cell-specific AR-/y mice and total AR knockout male mice. The results provide clear in vivo evidence that androgen/AR signaling in Sertoli cells plays a direct important role in spermatogenesis and in Leydig cells plays an autocrine regulatory role to modulate Leydig cell steroidogenic function. Total AR knockout male mice have the most severe defects among these mice. These contrasting data with G-AR-/y mice suggest AR might have different roles in the various cells within testis to contribute to normal spermatogenesis and male fertility in mice.

Original languageEnglish
Pages (from-to)18975-18980
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number50
DOIs
Publication statusPublished - Dec 12 2006

Fingerprint

Androgen Receptors
Spermatogenesis
Fertility
Testis
Knockout Mice
Germ Cells
Leydig Cells
mouse AR protein
Sperm Count
Sertoli Cells
Sperm Motility
Epididymis
Meiosis
Cell Communication
Androgens
Alleles

Keywords

  • Germ cell
  • Knockout
  • Leydig cells
  • Sertoli cells

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Differential effects of spermatogenesis and fertility in mice lacking androgen receptor in individual testis cells. / Tsai, Meng Yin; Yeh, Shauh Der; Wang, Ruey Sheng; Yeh, Shuyuan; Zhang, Caixia; Lin, Hung Yun; Tzeng, Chii Ruey; Chang, Chawnshang.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 50, 12.12.2006, p. 18975-18980.

Research output: Contribution to journalArticle

Tsai, Meng Yin ; Yeh, Shauh Der ; Wang, Ruey Sheng ; Yeh, Shuyuan ; Zhang, Caixia ; Lin, Hung Yun ; Tzeng, Chii Ruey ; Chang, Chawnshang. / Differential effects of spermatogenesis and fertility in mice lacking androgen receptor in individual testis cells. In: Proceedings of the National Academy of Sciences of the United States of America. 2006 ; Vol. 103, No. 50. pp. 18975-18980.
@article{59e59facc65e473eb4d2db952713df4e,
title = "Differential effects of spermatogenesis and fertility in mice lacking androgen receptor in individual testis cells",
abstract = "Using a Cre-Lox conditional knockout strategy, we generated a germ cell-specific androgen receptor (AR) knockout mouse (GAR-/y) with normal spermatogenesis. Sperm count and motility in epididymis from AR -/y mice are similar to that of WT (G-AR+/y) mice. Furthermore, fertility tests show there was no difference in fertility, and almost 100{\%} of female pups sired by G-AR-/y males younger than 15 weeks carried the deleted AR allele, suggesting the efficient AR knockout occurred in germ cells during meiosis. Together, these data provide in vivo evidence showing male mice without AR in germ cells can still have normal spermatogenesis and fertility, suggesting the essential roles of AR during spermatogenesis might come from indirect cell- cell communication in a paracrine fashion. We then compared the consequences of AR loss in the spermatogenesis and fertility of G-AR-/y mice with two other testicular cell-specific AR-/y mice and total AR knockout male mice. The results provide clear in vivo evidence that androgen/AR signaling in Sertoli cells plays a direct important role in spermatogenesis and in Leydig cells plays an autocrine regulatory role to modulate Leydig cell steroidogenic function. Total AR knockout male mice have the most severe defects among these mice. These contrasting data with G-AR-/y mice suggest AR might have different roles in the various cells within testis to contribute to normal spermatogenesis and male fertility in mice.",
keywords = "Germ cell, Knockout, Leydig cells, Sertoli cells",
author = "Tsai, {Meng Yin} and Yeh, {Shauh Der} and Wang, {Ruey Sheng} and Shuyuan Yeh and Caixia Zhang and Lin, {Hung Yun} and Tzeng, {Chii Ruey} and Chawnshang Chang",
year = "2006",
month = "12",
day = "12",
doi = "10.1073/pnas.0608565103",
language = "English",
volume = "103",
pages = "18975--18980",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "50",

}

TY - JOUR

T1 - Differential effects of spermatogenesis and fertility in mice lacking androgen receptor in individual testis cells

AU - Tsai, Meng Yin

AU - Yeh, Shauh Der

AU - Wang, Ruey Sheng

AU - Yeh, Shuyuan

AU - Zhang, Caixia

AU - Lin, Hung Yun

AU - Tzeng, Chii Ruey

AU - Chang, Chawnshang

PY - 2006/12/12

Y1 - 2006/12/12

N2 - Using a Cre-Lox conditional knockout strategy, we generated a germ cell-specific androgen receptor (AR) knockout mouse (GAR-/y) with normal spermatogenesis. Sperm count and motility in epididymis from AR -/y mice are similar to that of WT (G-AR+/y) mice. Furthermore, fertility tests show there was no difference in fertility, and almost 100% of female pups sired by G-AR-/y males younger than 15 weeks carried the deleted AR allele, suggesting the efficient AR knockout occurred in germ cells during meiosis. Together, these data provide in vivo evidence showing male mice without AR in germ cells can still have normal spermatogenesis and fertility, suggesting the essential roles of AR during spermatogenesis might come from indirect cell- cell communication in a paracrine fashion. We then compared the consequences of AR loss in the spermatogenesis and fertility of G-AR-/y mice with two other testicular cell-specific AR-/y mice and total AR knockout male mice. The results provide clear in vivo evidence that androgen/AR signaling in Sertoli cells plays a direct important role in spermatogenesis and in Leydig cells plays an autocrine regulatory role to modulate Leydig cell steroidogenic function. Total AR knockout male mice have the most severe defects among these mice. These contrasting data with G-AR-/y mice suggest AR might have different roles in the various cells within testis to contribute to normal spermatogenesis and male fertility in mice.

AB - Using a Cre-Lox conditional knockout strategy, we generated a germ cell-specific androgen receptor (AR) knockout mouse (GAR-/y) with normal spermatogenesis. Sperm count and motility in epididymis from AR -/y mice are similar to that of WT (G-AR+/y) mice. Furthermore, fertility tests show there was no difference in fertility, and almost 100% of female pups sired by G-AR-/y males younger than 15 weeks carried the deleted AR allele, suggesting the efficient AR knockout occurred in germ cells during meiosis. Together, these data provide in vivo evidence showing male mice without AR in germ cells can still have normal spermatogenesis and fertility, suggesting the essential roles of AR during spermatogenesis might come from indirect cell- cell communication in a paracrine fashion. We then compared the consequences of AR loss in the spermatogenesis and fertility of G-AR-/y mice with two other testicular cell-specific AR-/y mice and total AR knockout male mice. The results provide clear in vivo evidence that androgen/AR signaling in Sertoli cells plays a direct important role in spermatogenesis and in Leydig cells plays an autocrine regulatory role to modulate Leydig cell steroidogenic function. Total AR knockout male mice have the most severe defects among these mice. These contrasting data with G-AR-/y mice suggest AR might have different roles in the various cells within testis to contribute to normal spermatogenesis and male fertility in mice.

KW - Germ cell

KW - Knockout

KW - Leydig cells

KW - Sertoli cells

UR - http://www.scopus.com/inward/record.url?scp=34948871606&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34948871606&partnerID=8YFLogxK

U2 - 10.1073/pnas.0608565103

DO - 10.1073/pnas.0608565103

M3 - Article

C2 - 17142319

AN - SCOPUS:34948871606

VL - 103

SP - 18975

EP - 18980

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

SN - 0027-8424

IS - 50

ER -