Proposal # 0613895 Regulation of Oocyte Develpment
In mammals, the final number of eggs, or oocytes, available for reproduction of the next generation is defined at birth. Establishment of this oocyte pool is essential for fertility. Mouse oocytes develop in clusters of cells that break apart into individual cells and become packaged into primordial follicles within a few days of birth. During this time only a subset of eggs ultimately survive. The remaining immature eggs die by a normal developmental process called programmed cell death. This phase of oocyte differentiation is poorly understood and molecules and mechanisms that regulate this stage of oocyte development have not been identified. Recently, estrogen treatment of neonatal mice was found to alter oocyte development by inhibiting the oocyte clusters from breaking apart and protecting cells from death suggesting that estrogen signaling may regulate egg development. The goal of the research described in this proposal is to understand the role of estrogen signaling in normal oocyte development. First, the way in which estrogen signals to oocytes will be examined using estrogen related compounds and mice lacking estrogen receptors. Second, the role of estrogen signaling in programmed cell death regulation will be explored using genetics and cell death inhibitors. Finally, target genes of estrogen signaling will be identified. Information from this work will aid in understanding normal oocyte differentiation. It will also contribute better understanding of mammalian infertility and ovarian cancer. In addition to its impact on developmental biology, the project will foster the education and training of future scientists through active participation of both undergraduate and graduate students.
