Premature ovarian failure in androgen receptor-deficient mice

Hiroko Shiina, Takahiro Matsumoto, Takashi Sato, Katsuhide Igarashi, Junko Miyamoto, Sayuri Takemasa, Matomo Sakari, Ichiro Takada, Takashi Nakamura, Daniel Metzger, Pierre Chambon, Jun Kanno, Hiroyuki Yoshikawa, Shigeaki Kato

Research output: Contribution to journalArticle

216 Citations (Scopus)

Abstract

Premature ovarian failure (POF) syndrome, an early decline of ovarian function in women, is frequently associated with X chromosome abnormalities ranging from various Xq deletions to complete loss of one of the X chromosomes. However, the genetic locus responsible for the POF remains unknown, and no candidate gene has been identified. Using the Cre/LoxP system, we have disrupted the mouse X chromosome androgen receptor (Ar) gene. Female AR-/- mice appeared normal but developed the POF phenotype with aberrant ovarian gene expression. Eight-week-old female AR-/- mice are fertile, but they have lower follicle numbers and impaired mammary development, and they produce only half of the normal number of pups per litter. Forty-week-old AR -/- mice are infertile because of complete loss of follicles. Genome-wide microarray analysis of mRNA from AR-/- ovaries revealed that a number of major regulators of folliculogenesis were under transcriptional control by AR. Our findings suggest that AR function is required for normal female reproduction, particularly folliculogenesis, and that AR is a potential therapeutic target in POF syndrome.

Original languageEnglish
Pages (from-to)224-229
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number1
DOIs
Publication statusPublished - 2006 Jan 3
Externally publishedYes

    Fingerprint

Keywords

  • Female physiology
  • Folliculogenesis
  • Kit ligand
  • Male hormone
  • Nuclear receptor

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Shiina, H., Matsumoto, T., Sato, T., Igarashi, K., Miyamoto, J., Takemasa, S., Sakari, M., Takada, I., Nakamura, T., Metzger, D., Chambon, P., Kanno, J., Yoshikawa, H., & Kato, S. (2006). Premature ovarian failure in androgen receptor-deficient mice. Proceedings of the National Academy of Sciences of the United States of America, 103(1), 224-229. https://doi.org/10.1073/pnas.0506736102