Regulation of ovarian follicular development and oocyte maturation

了解卵巢卵泡发育和卵母细胞成熟的机制可能有助于提高人类和动物的生育能力。我们最近进行了一系列的初步实验，以研究胶质细胞源性神经营养因子（GDNF）是否可能参与调节卵巢功能。我们的数据表明，GDNF及其共受体，“重排过程中的转化”（RET）酪氨酸激酶受体GDNF家族受体？1（GFR？- 1)都在卵泡发育过程中的卵母细胞和颗粒细胞中表达。我们打算进一步探讨这种生长因子以何种方式调节卵巢功能。我的NSERC发现研究计划的长期目标是研究参与卵巢卵泡发育和卵母细胞成熟调节的因素和机制。本研究的短期目标是验证GDNF在卵巢卵泡发育过程中调控颗粒细胞增殖、分化和卵母细胞成熟的假说，以及Bmi-1基因表达抑制因子在这一调控过程中的重要作用。 细胞和分子的方法将被用来解决以下目标：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影响; 2.明确GDNF调控卵母细胞和颗粒细胞功能的信号通路; 3.研究Bmi-1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影响; 4.探讨GDNF和Bmi-1是否协同调节卵巢功能。5.研究GDNF通路与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.