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2015年11月10日讯 /生物谷BIOON/ –近日，来自希伯来大学的研究人员在国际学术期刊JCI上发表了一项最新研究进展，他们的研究结果或可帮助医生对一种可造成女性不孕以及青春期障碍的疾病进行诊断，同时对相关治疗方法的开发具有一定启示。
哺乳动物卵巢不仅是形成卵细胞的生殖器官，同时还是可以产生激素的性腺，对女性生理机能和发育的多个方面具有调节作用。但是人们对于卵巢和卵细胞发育的过程仍了解较少。到目前为止科学家们只发现了几个参与卵巢发育的关键基因，而该领域的任何发现都可能为生殖及不孕研究领域带来重要影响。
在这项研究中，研究人员发现了四名存在血缘关系的表姐妹，虽然她们都拥有两条X染色体，她们看起来也像是正常女性，但她们都存在卵巢发育不全的情况。由于缺少性激素，她们不能正常进入青春期，并且都接受了激素替代治疗。
研究人员对这四名女性进行了外显子测序分析，发现她们在Nup107这个基因上存在突变，该突变在她们的正常亲属中并没有出现。之前研究已经证明Nup107基因能够编码一种参与核孔复合体形成的蛋白质分子。
为了探究这种基因突变是否与卵巢发育不全存在关联，研究人员构建了Nup107突变的果蝇模型，结果发现许多雌性果蝇都表现出显著的卵巢发育障碍情况，其余发生突变的雌性果蝇虽然可以产生卵细胞，但大部分卵细胞发育都存在异常，不能产生后代。
综上所述，这些结果证明了该突变的重要性，同时也说明Nup107基因在卵巢发育以及卵细胞形成过程中具有重要作用。（基因宝jiyinbao.com）
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A mutation in the nucleoporin-107 gene causes XX gonadal dysgenesis
Ariella Weinberg-Shukron1,2, Paul Renbaum1, Rachel Kalifa3, Sharon Zeligson1, Ziva Ben-Neriah4, Amatzia Dreifuss3, Amal Abu-Rayyan5, Noa Maatuk6, Nilly Fardian3, Dina Rekler3, Moien Kanaan5, Abraham O. Samson6, Ephrat Levy-Lahad1,2, Offer Gerlitz3, and David Zangen7
Ovarian development and maintenance are poorly understood; however, diseases that affect these processes can offer insights into the underlying mechanisms. XX female gonadal dysgenesis (XX-GD) is a rare, genetically heterogeneous disorder that is characterized by underdeveloped, dysfunctional ovaries, with subsequent lack of spontaneous pubertal development, primary amenorrhea, uterine hypoplasia, and hypergonadotropic hypogonadism. Here, we report an extended consanguineous family of Palestinian origin, in which 4 females exhibited XX-GD. Using homozygosity mapping and whole-exome sequencing, we identified a recessive missense mutation in nucleoporin-107 (NUP107, c.1339G>A, p.D447N). This mutation segregated with the XX-GD phenotype and was not present in available databases or in 150 healthy ethnically matched controls. NUP107 is a component of the nuclear pore complex, and the NUP107-associated protein SEH1 is required for oogenesis in Drosophila. In Drosophila, Nup107 knockdown in somatic gonadal cells resulted in female sterility, whereas males were fully fertile. Transgenic rescue of Drosophila females bearing the Nup107D364N mutation, which corresponds to the human NUP107 (p.D447N), resulted in almost complete sterility, with a marked reduction in progeny, morphologically aberrant eggshells, and disintegrating egg chambers, indicating defective oogenesis. These results indicate a pivotal role for NUP107 in ovarian development and suggest that nucleoporin defects may play a role in milder and more common conditions such as premature ovarian failure.