The role of KAT6A in regulating primordial follicle activation in mouse ovary.

Abstract

Follicle is a primary structural and functional unit within the mammalian ovary, encompassing a centrally positioned oocyte surrounded by pregranulosa cells. Primordial follicles constitute the ovarian reserve, the activated primary follicle represents the inception of follicular development in mammals. The intricate balance between primordial follicle dormancy and activation is pivotal for sustaining ovarian reproductive function; over-activation of the primordial follicle pool can result in premature ovarian failure among women. Although recent studies have revealed that several functional genes and pathways, such as mammalian target of rapamycin signaling, play roles in controlling the activation of primordial follicles, our understanding of the molecular networks regulating the activation progress is still incomplete. Here, using the mouse in vitro ovarian culture model, we identify a new role for K (lysine) acetyltransferase 6 A (KAT6A) in regulating the activation of primordial follicles in mice. Our results show that the expression of KAT6A is increased during primordial follicle activation in the oocytes. Disruption of KAT6A activity with two specific inhibitors significantly suppresses primordial follicle activation in cultured mouse ovaries. Furthermore, we find that KAT6A regulates processing body (P-body) signaling pathway and the expression levels of Ddx6 in oocytes. This suggests that KAT6A may promote primordial follicle activation by regulating the P-body signaling pathway. Collectively, our results elucidate that KAT6A plays a crucial role in controlling the activation of primordial follicles in the mammalian ovary.NEW & NOTEWORTHY The dynamic balance between primordial follicle dormancy and activation is important for the maintenance of ovarian reproductive function. Our results show that the expression of KAT6A is increased during primordial follicle activation in the oocytes. Using two inhibitors of KAT6A exhibited decreased speed of primordial follicles activation in cultured mouse ovaries, and Ddx6 expression was increased in oocytes. Collectively, our results reveal that KAT6A controls the activation of primordial follicles in the mammalian ovary.