Regulation of ovarian follicular development and oocyte maturation

了解卵泡发育和卵母细胞成熟的机制可能有助于提高人和动物的生育力。我们最近进行了一系列初步实验，以研究胶质细胞系衍生神经营养因子(GDNF)是否可能参与调控卵巢功能。结果表明，在卵泡发育过程中，GDNF及其辅受体、RET酪氨酸激酶受体GDNF家族受体-1(GFR-1)在卵母细胞和颗粒细胞中均有表达。我们打算进一步探索这种生长因子是如何调节卵巢功能的。我的NSERC发现研究计划的长期目标是研究参与调控卵巢卵泡发育和卵母细胞成熟的因素和机制。这一建议的短期目标是验证GDNF在卵泡发育过程中调节颗粒细胞增殖、分化和卵母细胞成熟的假设，以及基因表达抑制因子Bmi-1在这一调节中起关键作用的假设。1.研究GDNF在卵泡发育过程中对颗粒细胞增殖、分化和卵母细胞成熟的作用；2.明确GDNF调控卵母细胞和颗粒细胞功能的信号通路；3.探讨Bmi-1在卵泡发育过程中是否参与颗粒细胞的增殖、分化和卵母细胞成熟；4.探讨GDNF和Bmi-1是否协同调节卵巢功能。5.研究胶质细胞源性神经营养因子通路(S)与Bmi-1之间潜在相互作用的性质。

Understanding the mechanisms of ovarian follicular development and oocyte maturation may help to improve human and animal fertility. We have recently performed a set of preliminary experiments to study whether Glial cell line-derived neurotrophic factor (GDNF) may be involved in regulating ovarian function. Our data indicates that GDNF and its co-receptors, the "rearranged during transformation" (RET) tyrosine kinase receptor GDNF family receptor ?-1 (GFR?-1) are all expressed in both oocytes and granulosa cells during follicular development. We intend to further explore in what manner this growth factor regulate ovarian function. The long term goal of my NSERC discovery research program is to study the factors and mechanisms involved in the regulation of ovarian follicular development and oocyte maturation. The short term objective of this proposal is to test the hypothesis that GDNF regulates granulosa cell proliferation, differentiation and oocyte maturation during ovarian follicular development and that Bmi-1, a gene expression repressor, is essential in this regulation. Cellular and molecular approaches will be utilized to address the following aims: 1. To study the role of GDNF on granulosa cell proliferation, differentiation and oocyte maturation during follicular development in vitro; 2.To identify the signaling pathway that is involved in GDNF regulation of oocyte and granulosa cell function; 3.To examine whether Bmi-1 plays a role in granulosa cell proliferation, differentiation and oocyte maturation during follicular development in vitro; 4. To elucidate whether GDNF and Bmi-1 cooperate to regulate ovarian function. 5. To study the nature of the potential interactions between the GDNF pathway(s) and Bmi-1.