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 Cre͞LoxP 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.male hormone ͉ nuclear receptor ͉ female physiology ͉ folliculogenesis ͉ kit ligand

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