Premature Ovarian Failure in Androgen Receptor-deficient Mice

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2005 Dec 24

PMID 16373508

Citations 113

Authors

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

Affiliations

Soon will be listed here.

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.

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