Table 1.

Properties of primordial follicles regulation mechanisms.

Mechanism	Major Participants	Mode of Action	Inhibitors	References
PI3K	PI3K, PTEN, Akt, MTOR, FOXO3a	Intracellular signal transduction, activated in response to extracellular signals; promotes proliferation, cell survival, and growth mediated through serine/threonine phosphorylation of downstream proteins	MTOR inhibitors such as Rapamycin, Temsirolimus, Everolimus, INK128, AS101	[9,10,11,12,13,14]
Hippo	YAP, TAZ, TEAD 1–4 CCN, BIRC	Intracellular signal transduction activated when physical disruption of ovarian cortex occurs. Involves a serine/threonine protein kinase cascade which impedes nuclear access of key effectors by phosphorylation and cytoplasmic retention mechanisms		[15,16,17,18]
c-jun	JNK, c-jun	Intracellular signal transduction pathway, regulates proliferation and apoptosis in the oocyte through JNK/c-Jun phosphorylation	JNK inhibitor VII	[19]
Erk 1/2	MAPK3/1, ERK1/2	ERK1/2 signaling is activated in pre-granulosa cells of the primordial follicle, leading to enhanced expression of KITL and then activation of PI3K pathway inside the oocyte	UO126	[20]
AMH	AMH, AMHR, SMAD 1/5/9	Secreted from early growing follicles in the ovary, suppresses primordial follicle activation through signal transduction. Most of the participants apart from SMAD 1/5/9 were not identified yet		[21,22,23]
ECM compression	ECM, pre-granulosa cells, oocytes nuclear rotation	Extracellular matrix together with surrounding pre-granulosa cells apply mechanical stress on PMF oocytes, inducing nuclear rotation, which keeps the PMF in dormant state		[24]
PMF cluster	Primordial follicles	Spatial features of primordial follicles, such as size, pattern of tissue distribution, and clustering, influence the fate of individual PMF to become activated or remain dormant		[25,26,27]