The dynamics of the primordial follicle reserve

Abstract

The female germline comprises a reserve population of primordial (non-growing) follicles containing diplotene oocytes arrested in the first meiotic prophase. By convention, the reserve is established when all individual oocytes are enclosed by granulosa cells. This commonly occurs prior to or around birth, according to species. Histologically, the 'reserve' is the number of primordial follicles in the ovary at any given age and is ultimately depleted by degeneration and progression through folliculogenesis until exhausted. How and when the reserve reaches its peak number of follicles is determined by ovarian morphogenesis and germ cell dynamics involving i) oogonial proliferation and entry into meiosis producing an oversupply of oocytes and ii) large-scale germ cell death resulting in markedly reduced numbers surviving as the primordial follicle reserve. Our understanding of the processes maintaining the reserve comes primarily from genetically engineered mouse models, experimental activation or destruction of oocytes, and quantitative histological analysis. As the source of ovulated oocytes in postnatal life, the primordial follicle reserve requires regulation of i) its survival or maintenance, ii) suppression of development (dormancy), and iii) activation for growth and entry into folliculogenesis. The mechanisms influencing these alternate and complex inter-related phenomena remain to be fully elucidated. Drawing upon direct and indirect evidence, we discuss the controversial concept of postnatal oogenesis. This posits a rare population of oogonial stem cells that contribute new oocytes to partially compensate for the age-related decline in the primordial follicle reserve.Reproduction (2013) 146 R205-R215

86 successful births and 9 ongoing pregnancies worldwide in women transplanted with frozen-thawed ovarian tissue: focus on birth and perinatal outcome in 40 of these children

“…OTC differs from other ART procedures like freezing oocytes or embryos by cryopreserving intact tissue containing small non-growing follicles [1,2]. Although the cryoprotectant media used to freeze ovarian tissue resemble those media used for oocytes and embryos, there are often subtle differences [3,4].…”

A putative role for anti-Müllerian hormone (AMH) in optimising ovarian reserve expenditure

“…The efficacy of multiple processes, including primordial germ cell migration, oogonial proliferation, nurse-cell organelle transfer and oogonial incorporation into primordial follicles, all contribute to the initial primordial follicle count (Kerr et al 2013, Lei & Spradling 2016. Subsequent primordial follicle activation, programmed cell death and oocyte extrusion from the ovary are processes that further affect the size of the ovarian reserve at puberty (Wordinger et al 1990, Tingen et al 2009).…”

“…After the initial burst of oogonial proliferation, the cells begin meiosis, but the process is arrested in prophase-I (Jones & Lane 2013). The arrested oocytes initially form clusters and then become encapsulated in pre-granulosa cells, forming a structure known as the primordial follicle, which represents a dormant, non-growing state (Kerr et al 2013). Primordial follicle activation is the first step in the development and growth phase that eventually leads to the generation of a preovulatory follicle capable of releasing a viable oocyte (McGee & Hsueh 2000).…”

Loss of oocytes due to conditional ablation of Murine double minute 2 (Mdm2) gene is p53‐dependent and results in female sterility

“…The majority of these are small primordial follicles with some regularly initiating growth recognized by the multiplication of granulosa cells and the apparition of the antral cavity accompanying the progressive enlargement of the oocyte [2]. Most investigations have focused on mechanisms involved in oocyte loss when these are at the resting stage in primordial follicles [3], while few data are available about mechanisms involved at later stages during oocyte and follicular growth. At the primordial stage, the tumor-related protein 63 (TRP63/p63) has been clearly implicated in oocyte death in response to genotoxic insult such as radiation or chemotherapeutic agent [4][5][6].…”