Mouse ovarian germ cell cysts undergo programmed breakdown to form primordial follicles

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.