AbstractThe oocyte provides the foundation for a totipotent zygote and ensures the inheritance of genetic and epigenetic information to successive generations, but how the finite source of the oocyte pool is established is poorly understood. Reconstitution of oogenic processes in vitro from pluripotent stem cells provides a versatile experimental platform for refining our understanding of oogenesis. In the current project, I used the in vitro system to screen for genes governing the embryonic oocyte development and searched for the possibility of using the acquired knowledge to establish the drug discovery scheme for fertility enhancement. With the establishment of CRISPR-mediated gene knockout ES cell lines and the subsequent in vitro oogenesis culture, I analyzed the effects of disrupting newly identified oogenic genes. Based on the gene expression analysis and the phenotypes observed, the new genes appear to regulate oogenesis in six key categories: (i) the formation of homologous recombination during meiotic prophase, (ii) retrotransposon repression, (iii) transcription and chromatin modification, (iv) RNA structural modification, (v) folliculogenesis, and (vi) DNA methylation. Some signaling pathways regulated by the newly identified genes are covered in FDA-approved drug repositioning chemical library, and thus the results offer interesting opportunities for drug intervention scheme to regulate the oocyte number. In future, I will perform in vivo analysis of several gene knockout mice and further elucidate the gene functions under the physiological conditions and test out the possibility of drug intervention for fertility enhancement. はじめに卵子は生命継承の要であり，その形成異常は不妊や先天性疾患の原因となる．卵形成は胎生期から開始し，「全能性の附与」を支える卵子の機能は段階的に獲得されていく．また，卵子の前駆細胞で奈良県立医科大学医学部発生・再生医学講座・助教長岡 創So NagaokaNara Medical University― 117 ―卵巣オルガノイド作成技術を駆使した妊孕性拡張創薬Drug discovery for fertility enhancement via ovarian organoid technology
元のページ ../index.html#119