Bayne Rosemary A L, Martins da Silva Sarah J, Anderson Richard A
MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, University of Edinburgh Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK.
Mol Hum Reprod. 2004 Jun;10(6):373-81. doi: 10.1093/molehr/gah056. Epub 2004 Mar 25.
The process of primordial follicle formation is central to the determination of a woman's reproductive lifespan, and in humans occurs towards the end of mid-gestation. Gene knockout analysis in the mouse has shown that Figla, a transcription factor specifically expressed in germ cells, is essential for oocytes to survive and form primordial follicles. Our objective was to investigate whether a human homologue present in the genome database plays a similar role in human ovary development. Standard and real-time RT-PCR demonstrated that the human FIGLA gene is expressed in the fetal ovary but not by a range of other tissues, and that expression increases across mid-gestation, rising some 40-fold by the time of primordial follicle formation. The entire coding sequence was cloned and new exonic sequences identified. Electrophoretic mobility shift assays with in vitro-expressed human FIGLA protein showed that, as in the mouse, FIGLA can heterodimerize with E12 protein and bind to the E-box of the human ZP2 promoter. Similar mobility shifts were identified in human fetal ovary extracts. These results suggest that FIGLA is involved in continued oocyte survival as primordial follicles form in the human as in the rodent ovary.
原始卵泡形成过程对于女性生殖寿命的决定至关重要,在人类中此过程发生于妊娠中期接近尾声时。对小鼠进行的基因敲除分析表明,Figla作为一种在生殖细胞中特异性表达的转录因子,对于卵母细胞存活并形成原始卵泡至关重要。我们的目标是研究基因组数据库中存在的人类同源物在人类卵巢发育中是否发挥类似作用。标准及实时RT-PCR结果显示,人类FIGLA基因在胎儿卵巢中表达,但在一系列其他组织中不表达,且其表达在妊娠中期升高,到原始卵泡形成时增加约40倍。克隆了完整编码序列并鉴定出了新的外显子序列。用体外表达的人类FIGLA蛋白进行的电泳迁移率变动分析表明,与小鼠情况一样,FIGLA能与E12蛋白形成异源二聚体并结合至人类ZP2启动子的E盒。在人类胎儿卵巢提取物中也鉴定出了类似的迁移率变动。这些结果表明,如同在啮齿动物卵巢中一样,在人类原始卵泡形成过程中FIGLA参与了卵母细胞的持续存活。