Ovarian development and maintenance are poorly understood; however, diseases that affect these processes can offer insights into their underlying mechanisms. XX Gonadal Dysgenesis (XX-GD) is a rare heterogeneous genetic disorder characterized by underdeveloped, dysfunctional ovaries, with a subsequent lack of spontaneous pubertal development, primary amenorrhea, uterine hypoplasia, and hyper-gonadotropic hypogonadism. Using homozygosity mapping and whole exome sequencing, we identified a missense recessive mutation in Nucleoporin107 (Nup107) in a consanguineous family with multiple females affected by XX-GD (with no other apparent developmental deficits). Nup107 is an essential component of the nuclear pore complex. We use Drosophila as a model to study the potential function of Nup107 in human female gonadal dysgenesis. A deletion allele of Nup107 is embryonically lethal in the fly, but can be rescued by exogenously expressing WT Nup107. Transgenic expression of the functionally equivalent Drosophila Nup107 missense mutation in flies, while rescuing viability, results in abnormal ovarian development accompanied by an almost complete sterility with a marked reduction in progeny, morphologically aberrant eggshells, disintegrating egg chambers and increased apoptosis, indicating defective oogenesis. RNAi knockdown of Nup107 in somatic gonadal cells causes complete female sterility, whereas males remain fully fertile. Interestingly, this specific RNAi knockdown in follicle cells causes defects in nurse cells and oocytes, both of which are germline cells. In contrast, specific knockdown of Nup107 in the germ line has no apparent effect in either sex. In summary, these results indicate Nup107 as a novel genetic source of ovarian dysgenesis and suggest that nucleoporin defects may play a role in milder and more common conditions such as premature ovarian failure. Future research using this XX-GD Drosophila model system will elucidate signaling pathways and new genes involved in both ovarian development and dysgenesis mechanisms.