Regulation of ovarian follicular development and oocyte maturation

点击翻译按钮获取中文摘要

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.