范可尼贫血(Fanconi anemia, FA)是一种罕见的常染色体或X染色体连锁的隐性遗传病,其发生源于范可尼贫血基因(FA基因)突变。FA基因是一组在DNA交联损伤中起同源重组修复作用的基因。FA女性患者常见早发性卵巢功能衰退(premature ovarian insufficient, POI)的特征,而FA小鼠也表现出生殖细胞严重缺乏,这些结果提示FA基因在哺乳动物卵泡发育中起重要作用。研究显示FA基因在促进原始生殖细胞增生,维持正常卵母细胞减数分裂,参与卵泡发育的促性腺激素调节以及卵母细胞与颗粒细胞生长过程中的相互调节等方面调节卵泡发育。本文综述了FA基因在卵泡发育中的作用和分子机制方面的研究进展,为POI的病因学解析提供遗传基础。

Fanconi anemia (FA) is a rare recessive autosomal or X-linked genetic disease caused by the mutations of the FA genes. The FA genes are involved in the homologous recombination repair processes of damaged interstrand crosslinks in DNA. Premature ovarian insufficiency (POI) is commonly observed in female FA patients and in mice of experimental FA models with serious deficiency of germ cells, suggesting that FA genes could play an important role(s) in follicle development in mammals. Studies have showed that FA genes play significant functions in promoting the proliferation of primordial germ cell, maintaining normal meiosis of the oocytes, participating in the gonadotropin regulation of oocytes and granular cell growth, and other aspects of regulation of follicular development. In this review, we summarize the roles and molecular mechanisms of FA genes in the development of mammalian follicle, which may provide some insights on the genetic basis for the etiology of POI.