Cellular and molecular regulation of the activation of mammalian primordial follicles: somatic cells initiate follicle activation in adulthood

Hum Reprod Update. Nov-Dec 2015;21(6):779-86. doi: 10.1093/humupd/dmv037. Epub 2015 Jul 30.


Background: The first small follicles to appear in the mammalian ovaries are primordial follicles. The initial pool of primordial follicles serves as the source of developing follicles and oocytes for the entire reproductive lifespan of the animal. Although the selective activation of primordial follicles is critical for female fertility, its underlying mechanisms have remained poorly understood.

Methods: A search of PubMed was conducted to identify peer-reviewed literature pertinent to the study of mammalian primordial follicle activation, especially recent reports of the role of primordial follicle granulosa cells (pfGCs) in regulating this process.

Results: In recent years, molecular mechanisms that regulate the activation of primordial follicles have been elucidated, mostly through the use of genetically modified mouse models. Several molecules and pathways operating in both the somatic pfGCs and oocytes, such as the phosphatidylinositol 3 kinase (PI3K) and the mechanistic target of rapamycin complex 1 (mTORC1) pathways, have been shown to be important for primordial follicle activation. More importantly, recent studies have provided an updated view of how exactly signaling pathways in pfGCs and in oocytes, such as the KIT ligand (KL) and KIT, coordinate in adult ovaries so that the activation of primordial follicles is achieved.

Conclusions: In this review, we have provided an updated picture of how mammalian primordial follicles are activated. The functional roles of pfGCs in governing the activation of primordial follicles in adulthood are highlighted. The in-depth understanding of the cellular and molecular mechanisms of primordial follicle activation will hopefully lead to more treatments of female infertility, and the current progress indicates that the use of existing primordial follicles as a source for obtaining fertilizable oocytes as a new treatment for female infertility is just around the corner.

Keywords: KIT; KIT ligand; PI3 kinase signaling; mechanistic target of rapamycin complex 1; primordial follicle activation; primordial follicle granulosa cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Female
  • Granulosa Cells / cytology*
  • Humans
  • Mammals / physiology
  • Mechanistic Target of Rapamycin Complex 1
  • Models, Biological*
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism
  • Multiprotein Complexes / physiology
  • Oocytes / physiology
  • Ovarian Follicle / cytology
  • Ovarian Follicle / metabolism
  • Ovarian Follicle / physiology*
  • Ovary / metabolism
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphatidylinositol 3-Kinases / physiology
  • Signal Transduction
  • Stem Cell Factor / genetics
  • Stem Cell Factor / metabolism
  • Stem Cell Factor / physiology
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism
  • TOR Serine-Threonine Kinases / physiology


  • Multiprotein Complexes
  • Stem Cell Factor
  • Phosphatidylinositol 3-Kinases
  • TOR Serine-Threonine Kinases
  • Mechanistic Target of Rapamycin Complex 1