[Frontiers in Bioscience 11, 126-135, January 1, 2006]

Stem cell factor (SCF)-Kit mediated phosphatidylinositol 3 (PI3) kinase signaling during mammalian oocyte growth and early follicular development

Kui Liu

Department of Medical Biochemistry and Biophysics, Umeå University, S-901 87, Umeå, Sweden

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. SCF, Kit and the PI3 kinase pathway
3.1. Kit and Kit ligand SCF
3.2. PI3 kinase
3.3. Akt and its activation
3.4. The FOXO subclass of forkhead box transcription factors
4. Kit-PI3 kinase signaling in mammalian oocytes
4.1. Kit and SCF in the mammalian ovary
4.2. Activation of the oocyte PI3 kinase pathway in mouse and rat oocytes by SCF
5. Mutant mouse models for the study of Kit-PI3 kinase pathway in oocytes
5.1. Spontaneously occurred Kit or SCF mutant mice
5.2. Kit Y719F mutant mice
5.3. Foxo3a deficient mice
5.4. GDF-9 deficient mice
6. Perspective
7. Acknowledgement
8. References

1. ABSTRACT

The bi-directional communication between mammalian oocytes and their surrounding granulosa cells has been shown to be crucial for ovarian follicular development. Studies on molecules derived from the oocytes, such as growth differentiation factor-9 (GDF-9) and bone morphogenetic protein-15 (BMP-15), have attracted great interest during the past decade, and it is common knowledge nowadays that these molecules participate in the bi-directional dialogue between the oocytes and their surrounding granulosa cells as well as follicular development. However, signaling molecules and pathways inside mammalian oocytes that control oocyte growth and early development of ovarian follicles, which may be monitored by factors produced by granulosa cells, have not been studied extensively. Based on our own data as well as ovarian phenotypes observed in several gene modified mice strains that were generated for studies of signal transduction, immunology and cancer, the current review focuses on the key features of the activation of oocyte phosphatidylinositol 3 kinase (PI3 kinase) pathway and its possible roles during mammalian oocyte growth and follicular development. We propose that the cascade from the granulosa cell-produced stem cell factor (SCF) to the oocyte surface SCF receptor Kit, and to the oocyte PI3 kinase pathway, may play an important role in the regulation of growth rate of mammalian oocytes, as well as in the activation and development of ovarian follicles.