Premature ovarian failure in androgen receptor-deficient mice
Premature ovarian failure in androgen receptor-deficient mice
复制标题
DOI：
10.1073/pnas.0506736102
复制
发表时间：
2006-01-03
影响因子：
11.1
通讯作者：
Kato, S
中科院分区：
文献类型：
--
作者：
Shiina, H;Matsumoto, T;Kato, S
卵巢早衰（POF）综合征是女性卵巢功能的早期下降，通常与X染色体异常有关，从各种Xq缺失到其中一条X染色体完全丢失。然而，负责POF的遗传位点仍然未知，也没有确定候选基因。利用Cre/LoxP系统，我们破坏了小鼠X染色体雄激素受体（Ar）基因。雌性AR（-/-）小鼠表现正常，但出现卵巢基因表达异常的POF表型。8周大的雌性AR（-/-）小鼠具有生育能力，但它们的卵泡数量较低，乳房发育受损，每窝产仔数仅为正常数量的一半。40周龄的AR（-/-）小鼠由于卵泡完全丧失而不育。来自AR（-/-）卵巢的mRNA全基因组微阵列分析显示，AR转录控制了卵泡发生的许多主要调节因子。我们的研究结果表明，AR功能是正常女性生殖，特别是卵泡发生所必需的，AR是POF综合征的潜在治疗靶点。
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.