FSH不同糖型对促性腺激素依赖期牛卵泡发育的调控作用及机制研究

促卵泡素（FSH）是超数排卵常用关键激素，其商品制剂生物学活性不稳定导致促卵泡发育效果个体差异大，严重影响超排效果，提高其生物学活性是破解该瓶颈关键。糖基化修饰对FSH生理功能至关重要，前期研究发现，低糖型FSH诱导牛颗粒细胞激素分泌和信号转导、促小鼠体内卵泡发育优于全糖型FSH，推测不同糖型FSH差异调控牛颗粒细胞和卵母细胞功能进而影响卵泡发育。项目拟研究全糖型和低糖型FSH对牛促性腺激素依赖期体外卵泡发育、颗粒细胞增殖、凋亡、激素分泌、卵母细胞发育潜能的作用，对卵泡发育基因调控网络和信号通路转导的影响；再结合超排程序，研究两种糖型FSH对牛体内卵泡发育、超排效果、激素分泌的作用，及对卵泡发育代谢产物和动力学的影响；最后结合体内外研究结果，阐明不同糖型FSH对卵泡发育的调控作用及机制，旨在拓展FSH糖基化修饰对卵泡发育调控的认知，为提高超排效果、生产高效重组FSH制剂提供理论和技术支撑。

Follicle stimulating hormone (FSH) is the hormone mainly and widely used for superovulation treatment. However, the significant bioactivity variations between each FSH hormone batch available in the current market, leads to the inconsistent and unpredictable superovulation outcomes. Improving the FSH bioactivity will greatly benefit the superovulation technique. Glycosylation of FSH is necessary for its ability to bind with its receptor and activate follicular development. Our previous studies showed that, compared with fully glycosylated FSH glycoform, hypo-glycosylated FSH glycoform significantly stimulated bovine granulosa cell steroidogenesis and downstream signaling pathways, and improved in vivo follicular development in a mouse model. These observations indicated that hypo- or fully glycosylated recombinant FSH may differentially regulate bovine follicular development via regulating follicular granulosa cell and oocyte development. In the proposed studies, we will identify hypo- and fully glycosylated FSH regulations on the gonadotropin-dependent in vitro follicular development, granulosa cell proliferation and apoptosis, hormone secretion, as well as oocyte in vitro maturation and developmental competence. Besides, we will also explore these two FSH glycoforms regulations on the gene expression network and cell signaling transduction related with follicular development. Then, by employing superovulation protocol, we will detect the 2 FSH glycoforms effects on the in vivo bovine follicular development, superovulation outcomes, and hormone secretion. The regulatory effects of FSH glycoforms on the follicle metabolisms and dynamics will also be elucidated. Finally, by combing the results from in vitro and in vivo studies, we will illuminate the regulatory effects and mechanism of different FSH glycoforms on bovine follicular development. The proposed studies will unveil the glycosylation regulation of FSH on follicular development, facility the high bioactivity recombinant FSH manufactory, and improve the superovulation outcomes.