Abstract
The mammalian ovary has two main functions—producing mature oocytes for fertilization and secreting hormones for maintaining the ovarian endocrine functions. Both functions are vital for female reproduction. Primordial follicles are composed of flattened pre-granulosa cells and a primary oocyte, and activation of primordial follicles is the first step in follicular development and is the key factor in determining the reproductive capacity of females. The recent identification of the phosphatidylinositol 3 kinase (PI3K)/phosphatase and tensin homolog deleted on chromosome 10 (PTEN) signaling pathway as the key controller for follicular activation has made the study of primordial follicle activation a hot research topic in the field of reproduction. This review systematically summarizes the roles of the PI3K/PTEN signaling pathway in primordial follicle activation and discusses how the pathway interacts with various other molecular networks to control follicular activation. Studies on the activation of primordial follicles have led to the development of methods for the in vitro activation of primordial follicles as a treatment for infertility in women with premature ovarian insufficiency or poor ovarian response, and these are also discussed along with some practical applications of our current knowledge of follicular activation.
Highlights
A small proportion of primordial follicles are recruited into the growing follicle pool [16,23], and the phosphatidylinositol 3 kinase (PI3K)/phosphatase and tensin homolog deleted on chromosome 10 (PTEN) signaling pathway in oocytes plays a critical role in primordial follicle activation [24]
The PI3K/PTEN Signaling in Oocytes Governs the Primordial Follicle Activation
Anotherstudy studyfrom fromLiu’s showedthat that conditional conditionalknockout knockoutof ofRptor regulatory protein complex in pre-granulosa cells can inactivate mechanistic target of rapamycin complex 1 (mTORC1) signaling, and regulatory protein complex 1) in pre-granulosa cells can inactivate mTORC1 signaling, this suppresses follicular activation and prevents the awakening of dormant oocytes [27,58]. This suppresses follicular activation and prevents the awakening of dormant oocytes the inactivation of mTORC1 activity by deletion of Rptor in oocytes does not affect follicular development or female reproductive capacity [59]. These results suggest that mTORC1 signaling in pre-granulosa cells is essential for the activation of primordial follicles
Summary
A large number of primordial follicles progressively occupy more peripheral parts of the ovary to create the primordial follicle pool [6], and the primordial follicle pool is considered to be the only source of germ cells for fertilization [5]. This theory has been challenged over the past decade [7,8], the latest research by Zhang et al supports the traditional view that no follicular renewal occurs in postnatal life in mice and humans [9,10]. The quantity and quality of the primordial follicle pool determine the length of reproductive life [16,17], and menopause occurs in human females when the number of primordial follicles drops below approximately 1000 [18]
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