p300 maintains primordial follicle activation by repressing <i>VEGFA</i> transcription

During the reproductive life, most primordial follicles (PFs) remain dormant for years or decades, while some are progressively activated for development. Misactivation of primordial follicles can cause ovarian diseases, for example, premature ovarian insufficiency (POI). Our results show that p300 expression increased with primordial follicle activation. Using a p300 inhibitor resulted in premature activation of primordial follicles in cultured mouse ovaries. Conversely, the ratio of primordial follicle activation was markedly decreased upon culturing with the p300 agonist. Furthermore, p300 regulated primordial follicle activation by inhibiting <i>Vegfa</i> transcription in granulosa cells. In addition, this study was extended to potential clinical applications, showing that short-term treatment with a p300 inhibitor in vitro significantly increased primordial follicle activation in newborn mouse ovaries after the renal subcapsular transplantation in female NSG mice. Our results revealed that p300 controls the activation of primordial follicles in mammalian ovaries.<b>NEW & NOTEWORTHY</b> In this study, our results show that p300 expression increases with primordial follicle activation. A p300 inhibitor results in premature activation of primordial follicles in cultured mouse ovaries. Conversely, the ratio of primordial follicle activation markedly decreases upon culturing with the p300 agonist. Furthermore, p300 regulates primordial follicle activation by inhibiting <i>Vegfa</i> transcription in granulosa cells.