Abstract for presentation at 11th International Congress of Human Genetics

Oocytes are the transgenerational stem cells that provide continuity of species, but ironically, from an initial maximum at birth, ovarian follicle dynamics lead to oocyte depletion by a slow process of maturation and selection, ultimately associated with failure of reproductive competence and menopause. We have studied the course of gene activity during follicle formation and maintenance, and defects that can limit reproductive lifespan. Oocytes themselves undergo an aging process that we have characterized by expression profiling. At the level of follicle differentiation, we have recently further analyzed in detail an instance of genetic control of menopause and premature ovarian failure. We have found evidence that both ovarian follicle formation and the maintenance of female fertility are partly based on continuous action of the transcription factor Foxl2. In its absence, follicle formation stops at a defined stage, and ovary-to-testis sex reversal is then initiated. This provides an entry point for understanding developmental mechanisms that sustain reproduction and suggests a possible role for sex determination genes in cessation of female reproductive life.