cAMP controls the balance between dormancy and activation of primordial follicles in mouse ovaries

Abstract

In mammalian ovaries, the balance between dormancy and activation of primordial follicles determines the female fecundity and endocrine homeostasis. Recently, several functional molecules and pathways have been reported to be involved in the activation of primordial follicles. However, the homeostasis regulatory mechanisms of primordial follicle activation are still scant. Our previous study has proved that a relatively higher concentration of cyclic AMP (cAMP) is required for primordial follicle formation. Here, we identified that cAMP also plays a vital role in the balance between dormancy and activation of primordial follicles. Our results showed that the concentration of cAMP remained stable in neonatal mouse ovaries, which is due to ADCY3, the synthetase of cAMP, and PDE3A, the hydrolytic enzyme of cAMP, were synchronously increased during the activation of primordial follicles in mouse ovaries. Once the concentration of cAMP in neonatal ovaries was either elevated or reduced in vitro, the activation of primordial follicles was either accelerated or decelerated accordingly. In addition, a higher concentration of cAMP in the ovaries of puberty mice improved primordial follicle activation in vivo. Finally, cAMP promoted primordial follicle activation via canonical mTORC1-PI3K signaling cascades and PKA signaling. In conclusion, our findings reveal that the concentration of cAMP acts as a key regulator in balancing the dormancy and activation of primordial follicles in the mouse ovary.

ADCY3: the pivotal gene in classical ketogenic diet for the treatment of epilepsy

“…We found that ADCY3 (adenylate cyclase 3) is an activator of cAMP. Increased expression of ADCY3 can catalyze ATP to generate cAMP, which then binds to the regulatory subunits of PKA, activating the catalytic subunits of PKA and subsequently activating PKA ( Hong et al, 2013 ; Zheng et al, 2023 ). Therefore, regulating the activity of cAMP plays a crucial role in controlling the excitability of neurons and networks ( Zhang et al, 2021b ).…”

ROCK1 is a multifunctional factor maintaining the primordial follicle reserve and follicular development in mice

“…3, I – N ). We further investigated the effect of ROCK1 on follicular development using a model of ovarian topical administration in vivo ( 21 , 22 ). The ovaries of 3-wk-old mice were given local in vivo injections of matrigel containing Y-27632, and ovaries were collected 2 wk after injection ( Fig.…”

“…Typical ovarian administration was performed according to the previous report ( 21 , 22 ). Briefly, 3-wk-old CD-1 female mice were anesthetized with avertin (300 mg/kg, T48402, Sigma), and the ovaries were gently exposed from the incisions on the backs, as illustrated in Supplemental Fig.…”

HDAC6-dependent deacetylation of NGF dictates its ubiquitination and maintains primordial follicle dormancy

“…Other factors playing essential roles in primordial follicle activation and follicular reserve maintenance include pre-granulosa cell-driven factors, such as KIT Ligand (KITL), mechanistic target of rapamycin kinase (mTOR), forkhead box l2 (FOXL2), SMAD family member 3 (SMAD3) and WNT [20][21][22][23]. Also, participation of cyclin dependent kinase inhibitor 1B (CDKNIB), HIPPO, nerve growth factor (NGF), transforming growth factor-beta (TGF-β), Rhoassociated coiled-coil containing protein kinase 1 (ROCK1), cyclin AMP (cAMP), and Sirtuin 1 (SIRT1) has been reported in primordial follicle activation and reserve maintenance [24][25][26][27][28][29][30][31][32].…”