Follicle formation and oocyte death

Introduction This chapter will focus on the development of primordial germ cells (PGCs) into oocytes and their subsequent assembly into primordial follicles that is essential for reproductive success (Figure 4.1). In the mouse, PGCs migrate to the genital ridge and begin dividing rapidly by mitosis [1]. These oogonia remain connected, through incomplete cytokinesis, in clusters of synchronously dividing cells known as germline cysts [2]. The oogonia then begin to enter meiosis and arrest in the diplotene stage of prophase I. Around the same time, germ cell cysts begin to break apart [3]. As these cysts separate, many oocytes are lost by apoptosis while others are surrounded by a single layer of granulosa cells, forming primordial follicles [4]. It is believed that improper regulation of cyst breakdown and primordial follicle formation can lead to fertility disorders such as premature ovarian insufficiency and primary amenorrhea, where an early depletion of oocytes leads to infertility [5, 6]. In addition, aberrant regulation of oocyte death as primordial follicles form may be the underlying cause of ovarian dysgerminoma, or germ cell tumors [7]. Little is known about what molecules regulate cyst breakdown, primordial follicle formation, and oocyte death. Elucidation of mechanisms regulating cyst breakdown, oocyte numbers, and primordial follicle formation is important because it will lead to the development of early screening and interventions for infertility and germ cell cancers.