The ovary is the first organ to age, culminating in a life stage known as menopause. This event not only marks the end of fertility, but it also launches drastic fluctuations in systemic health that then accelerates aging of other organs. Remarkably, the timeline for ovarian aging is destined before birth in the form of the ovarian reserve, which is defined by the number of primordial follicles. Formation of too few or early demise of primordial follicles hastens ovarian aging leading to early menopause and premature ovarian insufficiency. The development of the ovarian reserve occurs during fetal development in mammals and across animal phyla. Initially, oocytes exist in clusters called germline cysts. At midgestation in humans, and late in gestation and shortly after birth in mice, germline cyst breakdown occurs, which includes a massive transfer of cytoplasmic cargo, including organelles such as Golgi, from donor oocytes to neighboring oocytes via intercellular bridges. Donor oocytes die while acceptor oocytes grow and become surrounded by pre-granulosa cells to form primordial follicles. Previously, we discovered that expression of two Iroquois family homeobox transcription factors, IRX3 and IRX5, direct oocyte—pre-granulosa cell interactions critical to establishing robust primordial follicles that are equipped to transition into mature follicles with healthy oocytes. Additional studies have uncovered that IRX3/5 interact with cytoskeletal components to compartmentalize the oocyte cytoplasm. Further, live imaging studies exposed oocyte membrane and cytoplasmic infrastructure that highlight dynamic movement and interactions between neighboring oocytes and between oocyte and pregranulosa cells. Take together, these discoveries expose an early view of the innerworkings of oocyte machinery and cell-cell interactions that culminate in formation of nascent primordial follicles and establishes the ovarian reserve.