Premature ovarian failure in androgen receptor-deficient mice. - Archive ouverte HAL Access content directly
Journal Articles Proceedings of the National Academy of Sciences of the United States of America Year : 2006

Premature ovarian failure in androgen receptor-deficient mice.

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Hiroko Shiina
  • Function : Author
Takahiro Matsumoto
  • Function : Author
Takashi Sato
  • Function : Author
Katsuhide Igarashi
  • Function : Author
Junko Miyamoto
  • Function : Author
Sayuri Takemasa
  • Function : Author
Matomo Sakari
  • Function : Author
Ichiro Takada
  • Function : Author
Takashi Nakamura
  • Function : Author
Jun Kanno
  • Function : Author
Hiroyuki Yoshikawa
  • Function : Author
Shigeaki Kato
  • Function : Author

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.

Dates and versions

hal-00188143 , version 1 (15-11-2007)

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Hiroko Shiina, Takahiro Matsumoto, Takashi Sato, Katsuhide Igarashi, Junko Miyamoto, et al.. Premature ovarian failure in androgen receptor-deficient mice.. Proceedings of the National Academy of Sciences of the United States of America, 2006, 103 (1), pp.224-9. ⟨10.1073/pnas.0506736102⟩. ⟨hal-00188143⟩
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