A central dogma of reproductive biology has been that mammalian females lose the capacity for oogenesis during fetal development, such that a non-renewable stockpile of oocytes is endowed in the ovaries at birth. This reserve of oocytes is depleted during juvenile and adult life, eventually leaving the ovaries barren of genn cells. In humans, exhaustion of the oocyte pool occurs around the fifth decade of life, driving the menopause. In 2004, we published a study with mice that challenged this dogma [1]. Follow-up work not only supported this earlier study but also suggested a possible extra-ovarian source of oocyte-producing stem cells in adult females [2]. Specifically, we showed that bone marrow (BM)- derived cells express several germline markers and that BM transplantation (BMT) rescues oocyte production in adult mice rendered sterile by chemotherapy (busulfan plus cyclophosphamide) or a genetic mutation {Atm gene knockout). Cell tracking confirmed the presence of donor-derived immature oocytes in ovaries of transplanted females [2]. The PI therefore hypothesized that ovarian failure in aging females results from an age-related decline in the number or function of oocyte-producing stem cells (hereafter referred to as germline stem cells or GSCs) in adult females, or an age-related deterioration of the ovarian environment that impairs the ability of BM-derived germ cells to support oogenesis.
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