Research Progress and Clinical Application of Molecular Regulatory Mechanisms for the Formation, Maintenance, and Activation of the Primordial Follicles

The follicle is the basic unit of the ovary, consisting of a centrally located oocyte and the surrounding somatic cells (granulosa cells and theca). In mammals, primordial follicles are formed in limited numbers before or after birth. These follicles remain dormant for most of the time, comprising the ovarian reserve and supplying mature oocytes during a female’s reproductive life. Activation of primordial follicles into growing stage is referred as the initial follicle recruitment. The dynamic balance between dormancy and activation of primordial follicles is crucial for maintaining ovarian reproductive function, while premature depletion of the primordial follicle pool due to various factors may lead to premature ovarian insufficiency in females. This review outlines the importance of the events leading to the establishment of the ovarian reserve and highlights the fundamental factors and molecular networks known to influence primordial follicle activation in mouse. This review provides a comprehensive overview of the development and clinical application of in vitro activation of primordial follicles for the treatment of infertility in patients with premature ovarian insufficiency or ovarian dysfunction. Other research progress in the manipulation of the primordial follicle pool aimed at delaying ovarian aging and fertility preservation is also discussed.