The impact of oocyte death on mouse primordial follicle formation and ovarian reserve

Abstract

Background Ovaries, the source of oocytes, maintain the numbers of primordial follicles, develop oocytes for fertilization and embryonic development. Although it is well known that about two‐thirds of oocytes are lost during the formation of primordial follicles through cyst fragmentation and the aggregation of oocytes within the cyst, the mechanism responsible for this remains unclear. Methods We provide an overview of cell death that is associated with the oocyte cyst breakdown and primordial follicle assembly along with our recent findings for mice that had been treated with a TNFα ligand inhibitor. Main Findings It is generally accepted that apoptosis is the major mechanism responsible for the depletion of germ cells. In fact, a gene deficiency or the overexpression of apoptosis regulators can have a great effect on follicle numbers and/or fertility. Apoptosis, however, may not be the only cause of the large‐scale oocyte attrition during oocyte cyst breakdown, and other mechanisms, such as aggregation, may also be involved in this process. Conclusion The continued study of oocyte death during primordial follicle formation could lead to the development of novel strategies for manipulating the primordial follicle pool, leading to improved fertility by enhancing the ovarian reserve.

CD38 regulates ovarian function and fecundity via NAD+ metabolism

“…Female mice and humans are born with a fixed number of primordial follicles, also known as the ovarian reserve, which intrinsically determines the timeline of female reproductive longevity and fertility by virtue of the size of the initial follicular reserve and the rate of follicular death or maturation. 39 The initial formation of the ovarian reserve is a complex embryonic developmental process and it occurs during the early stages of oogenesis which involves germ cell cyst formation, organelle donation, and eventual cyst breakdown to form the primordial follicle reserve. 40 The timeline for mouse oogenesis differs between genetic mouse strains, but the C57BL6J strain undergoes complete cyst breakdown by postnatal-day-two (P2).…”

Transcriptomic Signatures of WNT-Driven Pathways and Granulosa Cell-Oocyte Interactions during Primordial Follicle Activation

“…The process of primordial follicle assembly in mice takes place from before birth to postnatal day (PD) 5, followed by the growth of activated primordial follicles starting from PD6 [16][17][18]. Ovarian samples were collected from wild-type and from Wls cKO mice at PD7, with an assumption that the cell populations around the transition from primordial to primary follicles were abundantly present.…”

CD38 regulates ovarian function and fecundity via NAD+metabolism

“…To further investigate why reproductively young CD38 KO mice have a larger number of primordial follicles, we investigated neonatal stages of ovarian development when the ovarian reserve is established. Female mice and humans are born with a fixed number of primordial follicles, also known as the ovarian reserve, which intrinsically determines the timeline of female reproductive longevity and fertility by virtue of the size of the initial follicular reserve and the rate of follicular death or maturation 37 . The initial formation of the ovarian reserve is a complex embryonic developmental process and it occurs during the early stages of oogenesis which involves germ cell cyst formation, organelle donation, and eventual cyst breakdown to form the primordial follicle reserve 38 .…”