In many organisms, early germline development takes place within cysts of interconnected cells that form by incomplete cytokinesis and later undergo programmed breakdown. We recently identified similar cell clusters within the fetal mouse ovary, but the fate and functional significance of these germ cell cysts remained unclear. Here, we show that mouse cysts undergo programmed breakdown between 20.5-22.5 dpc, during which approximately 33% of the oocytes survive to form primordial follicles. This process accounts for most of the perinatal reduction in germ cell numbers and germ cell apoptosis reported by previous authors, and suggests that perinatal germ cell loss is a developmentally regulated process that is distinct from the follicular atresia that occurs during adult life. Our observations also suggest a novel function for a transient cyst stage of germ cell development. Prior to breakdown, mitochondria and ER reorganize into perinuclear aggregates, and can be seen within the ring canals joining adjacent germ cells. Cysts may ensure that oocytes destined to form primordial follicles acquire populations of functional mitochondria, through an active process that has been evolutionarily conserved.

In mammals, the final number of oocytes available for reproduction of the next generation is defined at birth. Establishment of this oocyte pool is essential for fertility. Mammalian primordial germ cells form and migrate to the gonad during embryonic development. After arriving at the gonad, the germ cells are called oogonia and develop in clusters of cells called germ line cysts or oocyte nests. Subsequently, the oogonia enter meiosis and become oocytes. The oocyte nests break apart into individual cells and become packaged into primordial follicles. During this time, only a subset of oocytes ultimately survive and the remaining immature eggs die by programmed cell death. This phase of oocyte differentiation is poorly understood but molecules and mechanisms that regulate oocyte development are beginning to be identified. This review focuses on these early stages of female germ cell development.