中文摘要
在本课题前期研究的基础上,旨在探讨促性腺激素调控卵母细胞减数分裂成熟过程中遗传和表观遗传学改变的机制,阐明其导致卵母细胞非整倍性或印记基因异常的分子机理。以体内促排和自然周期的小鼠和体外人卵母细胞成熟培养模型为研究载体,检测促性腺激素对卵母细胞减数分裂成熟的细胞学指标以及细胞周期调控的重要基因,特别是对检验点基因的表达,印记基因的甲基化及相关基因的检测等,来探讨促性腺激素对染色体非整倍体发生、表观遗传改变等的影响机制。并在此基础上开展EGF-BDNF-IGF-1用于人卵母细胞体外成熟培养的应用基础研究,探讨其改善卵母细胞质量和发育潜能,以及可能的保护机制,探讨其安全性,为临床转化寻找佐证。本研究将有助于深入了解促性腺激素的临床作用机制,并为EGF-BDNF-IGF-1临床转化应用打下基础,有助于增加辅助生育技术中卵母细胞的发育潜能,减少促性腺激素治疗风险的发生。
英文摘要
Based on our previous studies in this subject, the gonadotropin-mediated molecular mechanism of genetic and epigenetic on oocyte maturation in vitro and in vivo will be investigated in order to explain its cause on oocyte aneuploidy or abnormal molecular imprinted genes mechanism. Oocytes from nature and stimulation cycle of mouse and human oocytes matured in vitro will be used as culture model for this study, which will investigate gonadotropin-mediated oocyte meiotic maturation and gene alteration related to cell cycle regulation, especially for checkpoint gene expression, methylation of imprinted genes, and further explore the mechanism of gonadotropin-caused chromosome aneuploidy and epigenetic alteration. Base on this design, the grow factors, EGF, BDNF and IGF-1 will be added into culture medium for human oocytes in vitro maturation, it will explore their impact on oocyte quality and developmental potential, and possible protective mechanism, finally evaluate growth factors’ safety for assisted reproduction clinical use. These studies will help to understand the clinical effect and mechanism of gonadotropin, and lay the foundation for the growth factors’ clinical applications, consequently helping to increase the developmental potential of oocytes, and reduce gonadotropin-induced risks during assisted reproductive technology.
